How do I know which genes are missing?

David March 5David decided to stand still so I could
take his picture.  Thanks David!

I often get asked to interpret a genetic report.  I am not a clinician of any sort. I never even had a genetics course.  But, there are certain skills one must pick up along the way to study which genes are missing in 22q13 deletion syndrome and what they do.  So, I have some idea how to read a report, just enough to accomplish my goals.

If you have a genetic report, here are some ways you, too, can figure out which genes are missing.  David only had a FISH test 15 years ago, so I don’t know how many genes he is missing.  You may be in much better shape. If you had an array or sequence done on your child, you should have enough information to find out which genes are missing.  Here is how.

Expert mode

The experts use the technical part of a genetic report to see what has been deleted. The technical part will often look something like this:
hg17  arr 22q13.33 (48,230,183-49,523,149) X1
This example is a simple terminal deletion of chromosome 22 (not a real case).  It says that part of chromosome 22 only has one copy (X1).  The nomenclature can get complicated if there are multiple genetic problems.  The nomenclature is outlined here:

Once you know which base-pairs are missing (48,230,183-49,523,149) and which genome assembly was used to make the measurement (hg17), you can go to the UCSC Genome Browser and get gobs of information about the deletion.  The Genome Browser is complicated to use, but I use it often. 


Sometimes the report provides a complete list of the missing genes.  “Complete” is relative to certain things.  For instance, most gene array studies cannot detect the presence or loss of the last gene on the chromosome, RABL2B.  This gene is too similar to RABL2A and no one thinks RABL2B is important enough to make a special effort to detect it. (I happen to disagree. See my blog Is 22q13 deletion syndrome a ciliopathy.) Otherwise, the gene list is useful.  If the only listed genes are SHANK3 and ARSA, the gene list is worthless.  It means the geneticist either did not want to look up, or share with you, the other genes that are missing.

End gene or deletion size

If the deletion is a terminal deletion, you can use the deletion size to look up the genes on my list (below).  If the report says something like, “from PLXNB2 to ACR” or “distal to” PLXNB2, then you can find PLXNB2 on the list and it becomes the marker for where the deletion starts. Terminal deletions start from the “end” gene and go up the list (down in gene number on my list).

Go to the Foundation’s web site?

If you had 18q deletion syndrome, there is a site that was created for parents to look up the genes that are missing and what those genes do.  No such site exists for 22q13.

Ask your geneticist

I have seen some very nice genetics reports with a complete list of genes deleted.  This is rare, but you might try asking for such a document.

The list

Here is a list of the genes that covers the last 9,300 Kb (9.3 Mb) of 22q13.  That is about the size of the largest known terminal deletion.  The list comes with a few caveats.  First, deletions can be messy.  Sometimes lots of genes are gone, then part of the subsequent gene is gone.  People don’t count half a gene.  They usually add the partial gene to the gene count. Micro arrays (gene chips) sample the genes every so many kilobases (Kb).  It is not a continuous readout of the DNA.  Thus, in most cases, you don’t know the exact position of the break.   DNA includes many things in addition to genes. It encodes things called microRNAs, and the DNA has essential gene promoter, inhibitor and enhancer regions within genes and between genes.  Thus, a gene list tells only part of the story.  Finally, I found an error in my list this past week, so let me know, but please don’t complain if this has more errors!  I will correct this page as I find errors.  However, I emphasize that this list comes without any warranty whatsoever.  I take no responsibility for its use.  It is part of a blog to educate parents.  It is not a tool for legal, medical or any other practice. Ok?
[updated/corrected 6 March 2016]
[updated/corrected 12 March 2016]
[updated/corrected 17 June 2016]
[updated/corrected 5 December 2016]
[updated/corrected 7 April 2017]
Table now shows the smallest distance to the gene. For example, a terminal deletion of size 196.0 Kbase will delete all the genes before ARSA and damage part of ARSA.  Table is now limited to 9.3 Mbase (9,300,000) which is the largest recorded terminal deletion.

#       Gene       Deletion size (Kbase) 
1       RABL2B        34.81 
2       ACR           78.11 
3       SHANK3        85.17 
4       ARSA         195.14 
5       MAPK8IP2     206.92 
6       CHKB         235.47 
7       CPT1B        240.05 
8       SYCE3        255.56 
9       KLHDC7B      267.45 
10      ODF3B        286.65 
11      TYMP         288.47 
12      SCO2         292.86 
13      NCAPH2       295.00 
14      LMF2         310.78 
15      MIOX         328.43 
16      ADM2         332.03 
17      SBF1         343.44 
18      PPP6R2       373.38 
19      DENND6B      491.41 
20      PLXNB2       539.63 
21      MAPK11       548.08 
22      MAPK12       557.16 
23      HDAC10       567.21 
24      TUBGCP6      573.90 
25      SELO         600.85 
26      TRABD        618.90 
27      PANX2        638.18 
28      MOV10L1      656.85 
29      MLC1         733.11 
30      TTLL8        763.84 
31      IL17REL      809.78 
32      PIM3         854.39 
33      CRELD2       895.76 
34      ALG12        900.01 
35      ZBED4        928.39 
36      BRD1         995.26 
37      C22orf34     1,160.96 
38      FAM19A5      2,067.65 
39      TBC1D22A     3,642.77 
40      CERK         4,080.21 
41      GRAMD4       4,180.53 
42      CELSR1       4,281.30 
43      TRMU         4,484.77 
44      GTSE1        4,487.66 
45      TTC38        4,543.18 
46      PKDREJ       4,555.11 
47      CDPF1        4,570.18 
48      PPARA        4,620.06 
49      PRR34        4,764.32 
50      WNT7B        4,841.34 
51      ATXN10       4,973.16 
52      FBLN1        5,287.14 
53      RIBC2        5,385.97 
54      SMC1B        5,404.90 
55      FAM118A      5,508.30 
56      UPK3A        5,522.59 
57      KIAA0930     5,577.70 
58      NUP50        5,630.45 
59      PHF21B       5,809.48 
60      ARHGAP8      5,955.68 
61      PRR5         6,080.79 
62      LDOC1L       6,320.17 
63      KIAA1644     6,505.62
64      PARVG        6,610.00 
65      PARVB        6,649.55 
66      SAMM50       6,821.94 
67      PNPLA3       6,870.90 
68      PNPLA5       6,926.46 
69      SULT4A1      6,955.97 
70      EFCAB6       7,248.33 
71      MPPED1       7,310.62 
72      SCUBE1       7,475.08 
73      TTLL12       7,631.34 
74      TSPO         7,655.23 
75      MCAT         7,675.07 
76      BIK          7,688.76 
77      TTLL1        7,729.13 
78      PACSIN2      7,942.26 
79      ARFGAP3      7,961.07 
80      A4GALT       8,123.48 
81      ATP5L2       8,177.87 
82      CYB5R3       8,173.96 
83      RNU12        8,203.08 
84      POLDIP3      8,203.60 
85      SERHL2       8,260.06 
86      RRP7A        8,298.67 
87      SERHL        8,305.91 
88      NFAM1        8,386.07 
89      TCF20        8,603.03 
90      CYP2D6       8,688.56 
91      NDUFA6       8,727.69 
92      SMDT1        8,735.12 
93      FAM109B      8,739.03 
94      NAGA         8,747.64 
95      WBP2NL       8,785.70 
96      SEPT3        8,828.88 
97      CENPM        8,871.30 
98      TNFRSF13C    8,891.65 
99      SHISA8       8,903.80 
100     SREBF2       8,911.16 
101     CCDC134      8,992.58 
102     MEI1         9,019.01 
103     C22orf46     9,124.62 
104     NHP2L1(SNU13)9,129.56 
105     XRCC6        9,154.43 
106     DESI1        9,197.37 
107     PMM1         9,228.58 
108     CSDC2        9,241.80 
109     POLR3H       9,273.98 
110     ACO2         9,289.48 

Check out my earlier blogs (below) to learn how many of your friends are missing a similar number of genes and which genes might be important.  If you find this information valuable, please leave me a positive comment, or repost the blog elsewhere (e.g., Facebook).  Many thanks to each parent who has shared his/her child’s information and shared their own very personal stories. Your contributions and feedback helps me feel that I am not alone in the quest to make the world a better place for our kids.


Previous blogs

Mouse models
Science Leadership
How can the same deletion have such different consequences?
22q13 and the hope of precision medicine
22q13 Deletion Syndrome: hypotonia
Understanding gene size
Gene deletions versus mutations: sometimes missing a gene is better.
Is 22q13 deletion syndrome a ciliopathy?
Understanding translocations in 22q13 deletion syndrome: genetics and evolution
Understanding deletion size
Can 22q13 deletion syndrome cause ulcerative colitis?
Can 22q13 deletion syndrome cause cancer?
22q13 deletion syndrome – an introduction


6 thoughts on “How do I know which genes are missing?

  1. I appreciate your knowledge. I appreciate your time and conversation when I found out about Miki’s second hit of ALG12 and the scientist that is studying the second hits in our kids, and the doctor that works at the same University as Dr Phelan. I appreciate your input as both a parent and as a scientist.


  2. Thank you, Andrew! This is very valuable, practical information. Our consult with the geneticist was useless – she told us Yulia’s deletion size was large (6.1 Mb) and when asked what that means we got “she’ll be OK.” True story. With your blog I can now actually make sense of the diagnosis and look up the 57 missing genes.


  3. Thank you very much for putting so much effort and time!!! I absolutely love your blog.
    According to our report, Angie has a terminal deletion size of 3.5Mb.
    So all the genes, including some part of the TBC1D22A gene are deleted, right?
    The report says:
    arr 22q13.31q13.33(47,630,481×2, 47,664,055-51,178,235×1~2)

    What does the x2 or X1~2 stands for? I’m guessing it states which base parts she has 2 copies of, and which are missing.
    She has mosaic and ring22



    • It is times like this that I wish I had taken a course in cytogenetics. I am not a geneticist or a clinician of any sort. I read what I need to know as a go. The bit of info missing from your report is the genome assembly. The terminal deletion range matches with hg38, so I will assume we can use that build. I hope someone qualified will correct me if I am wrong, but I suspect 47,630,481×2 means that was the last spot on the chromosome where only normal (2 copies) of 22q13.33 was found. Arrays used to test sample the chromosome at various intervals (probes). So the probe at 47,630,481 read normal. Following that, apparently the next probe and all subsequent probes found either one copy or two copies, as you had surmised. I still have not verified the nomenclature X1-2, but I agree that is probably a mosaic. That is, in some samples they found x1 and other samples they found x2. (It may be calculated statistically rather than looking at samples from individual cells.) I cannot tell if some of the ch22 is normal and some ring. The mosaic suggests a somatic mutation (after fertilization) rather than a germ line mutation. The one thing that has me stumped is the deletion size of 3.5 MB. I would venture the deletion is 3,154,414. Practically speaking, it does not change the number of genes lost. However, that DNA may have other regulatory elements of importance. Your daughter has lost BRD1 which is a very important regulatory gene. It is probably far more important than SHANK3. A group out of Denmark is studying it and most of their work has not been published yet. It has a different impact on males than females.


      • Thank you for the reply, and for excepting my friendship request 🙂
        They did several test, array and fish. Maybe the fish gave the ring result, I don’t remember.
        Anyway thank you for the info!
        And I would try to read more about BRD1.


  4. I don’t even know where to begin. This is amazing! This has helped more than you know. I so glad someone has taken time and put this into perspective for me. I’ve been wandering what all the genes mean. Thank you!


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