CSMD3

Summary

CSMD3 (CUB and Sushi multiple domains 3, HGNC:19291) is a protein-coding gene on chromosome 8q23.3, encoding CUB and sushi domain-containing protein 3 (Q7Z407). Involved in dendrite development.

Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma membrane.

Source: NCBI Gene 114788 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 21
• Clinical variants (ClinVar): 580 total (top 6% of genes corpus-wide)
• GTEx eGene: eQTL in 7 tissues, sQTL in 1 (q < 0.05)
• Cancer driver (intOGen): activating (oncogene-like) across 18 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 0.97 (loss-of-function intolerant), LOEUF 0.46 (moderately constrained)
• MANE Select transcript: NM_198123
• Notable: 580 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19291
Approved symbol	CSMD3
Name	CUB and Sushi multiple domains 3
Location	8q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164796
Ensembl biotype	protein_coding
OMIM	608399
Entrez	114788

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000297405

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 6, TSL 2: 2, TSL 3: 1, TSL 5: 1

ENST00000297405, ENST00000339701, ENST00000343508, ENST00000455883, ENST00000462254, ENST00000492692, ENST00000493303, ENST00000497026, ENST00000519485, ENST00000534172, ENST00001106193, ENST00001106194

RefSeq mRNA: 4 — MANE Select: NM_198123 NM_001363185, NM_052900, NM_198123, NM_198124

CCDS: CCDS6315, CCDS6316, CCDS6317

Canonical transcript exons

ENST00000297405 — 71 exons

Exon	Start	End
ENSE00001087542	112255254	112255427
ENSE00001087557	112263639	112263812
ENSE00001087561	112265411	112265590
ENSE00001087586	112337543	112337731
ENSE00001087593	112383567	112383663
ENSE00001087598	112390664	112390788
ENSE00001087599	112346097	112346213
ENSE00001087603	112472591	112472707
ENSE00001087609	112408318	112408413
ENSE00001201268	112287064	112287246
ENSE00001201313	112281174	112281350
ENSE00001291336	112406524	112406727
ENSE00001292210	112408919	112409032
ENSE00001295519	112506691	112506829
ENSE00001298292	112636817	112637005
ENSE00001298881	112352416	112352534
ENSE00001304025	112492489	112492683
ENSE00001306738	112550671	112550873
ENSE00001307820	112556763	112556954
ENSE00001310683	112638696	112638911
ENSE00001313565	112351175	112351244
ENSE00001315308	112517034	112517225
ENSE00001319430	112587066	112587235
ENSE00001320189	112380352	112380456
ENSE00001324568	112503790	112503977
ENSE00001327720	112552594	112552720
ENSE00001328227	112573501	112573657
ENSE00001338519	112289365	112289538
ENSE00001338520	112291510	112291695
ENSE00001338521	112292537	112292710
ENSE00001338522	112295833	112296006
ENSE00001338524	112301793	112301966
ENSE00001338526	112306007	112306192
ENSE00001338528	112310978	112311166
ENSE00001338535	112341477	112341686
ENSE00001338799	112645109	112645225
ENSE00001338801	112650161	112650349
ENSE00001338804	112656154	112656341
ENSE00001338807	112682442	112682636
ENSE00001338810	112685406	112685732
ENSE00001338813	112689868	112690050
ENSE00001338816	112800162	112800274
ENSE00001338818	112829686	112829789
ENSE00001338821	112859145	112859266
ENSE00001338822	112921627	112921751
ENSE00001340488	112947790	112947877
ENSE00001340489	112954684	112954761
ENSE00001340490	113019067	113019179
ENSE00001374942	112304721	112304915
ENSE00001382041	112975837	112976148
ENSE00001654237	112666277	112666415
ENSE00001850376	113436677	113436939
ENSE00001924906	112222928	112224930
ENSE00003468583	112335329	112335474
ENSE00003508574	112231545	112231632
ENSE00003520668	112228756	112228891
ENSE00003523375	112237190	112237348
ENSE00003525796	113098756	113098963
ENSE00003541532	113314571	113314793
ENSE00003593652	113173722	113173916
ENSE00003593844	112318837	112318950
ENSE00003603374	112314429	112314617
ENSE00003609061	112319901	112319981
ENSE00003612710	112247020	112247131
ENSE00003615817	112241720	112241785
ENSE00003625104	112336652	112336829
ENSE00003676836	112254253	112254326
ENSE00003677698	113278592	113278704
ENSE00003679078	112313906	112314052
ENSE00003684193	112234365	112234477
ENSE00003686676	112244394	112244573

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 91.63.

FANTOM5 (CAGE): breadth broad, TPM avg 7.0337 / max 1464.0687, expressed in 329 samples.

Highest expression (Bgee): middle temporal gyrus, Brodmann (1909) area 23, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, secondary oocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CSMD3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	1.5e-21	-0.77	8:113379745:A:G
Testis	sqtl	1.2e-11	-0.70	8:113050714:C:G
Brain Cerebellar Hemisphere	eqtl	1.6e-06	+0.62	8:113358269:G:A
Pituitary	eqtl	7.8e-05	+0.29	8:113733803:G:A
Brain Cerebellum	eqtl	1.0e-04	+0.59	8:113358269:G:A
Nerve Tibial	eqtl	1.4e-04	+0.16	8:113685505:A:AG
Testis	eqtl	1.9e-04	+0.22	8:112632796:C:T
Brain Hippocampus	eqtl	3.4e-02	+0.38	8:112921830:C:T

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
94459	6.5164	309
94461	0.2191	88
94457	0.0644	17
94465	0.0590	2
94462	0.0553	16
94463	0.0527	12
94460	0.0431	20
94455	0.0193	10
94464	0.0044	2

Top tissues by expression

showing 100 of 235 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	91.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.63	gold quality
secondary oocyte	CL:0000655	81.58	gold quality
cortical plate	UBERON:0005343	80.38	gold quality
primary visual cortex	UBERON:0002436	80.13	gold quality
endothelial cell	CL:0000115	78.63	silver quality
superior frontal gyrus	UBERON:0002661	75.28	gold quality
entorhinal cortex	UBERON:0002728	74.92	gold quality
occipital lobe	UBERON:0002021	74.52	gold quality
prefrontal cortex	UBERON:0000451	74.22	gold quality
corpus callosum	UBERON:0002336	72.99	gold quality
hypothalamus	UBERON:0001898	72.73	gold quality
temporal lobe	UBERON:0001871	72.65	gold quality
nucleus accumbens	UBERON:0001882	72.63	gold quality
neocortex	UBERON:0001950	72.40	gold quality
frontal cortex	UBERON:0001870	72.38	gold quality
cerebral cortex	UBERON:0000956	72.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.28	gold quality
postcentral gyrus	UBERON:0002581	71.96	gold quality
Ammon’s horn	UBERON:0001954	71.68	gold quality
Brodmann (1909) area 46	UBERON:0006483	71.47	gold quality
amygdala	UBERON:0001876	71.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.11	gold quality
anterior cingulate cortex	UBERON:0009835	70.55	gold quality
caudate nucleus	UBERON:0001873	69.90	gold quality
parietal lobe	UBERON:0001872	69.88	gold quality
forebrain	UBERON:0001890	68.86	gold quality
right frontal lobe	UBERON:0002810	68.79	gold quality
right testis	UBERON:0004534	68.69	gold quality
testis	UBERON:0000473	68.37	gold quality
left testis	UBERON:0004533	68.17	gold quality
brain	UBERON:0000955	67.67	gold quality
ventricular zone	UBERON:0003053	66.17	gold quality
embryo	UBERON:0000922	65.97	gold quality
ganglionic eminence	UBERON:0004023	65.97	gold quality
putamen	UBERON:0001874	65.63	gold quality
substantia nigra	UBERON:0002038	64.29	gold quality
superior vestibular nucleus	UBERON:0007227	63.97	gold quality
midbrain	UBERON:0001891	63.64	gold quality
pancreatic ductal cell	CL:0002079	63.15	silver quality
cerebellar cortex	UBERON:0002129	61.65	gold quality
cerebellar hemisphere	UBERON:0002245	61.49	gold quality
oocyte	CL:0000023	61.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	61.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	61.38	gold quality
cerebellum	UBERON:0002037	60.81	gold quality
vagina	UBERON:0000996	60.59	gold quality
spinal cord	UBERON:0002240	60.31	gold quality
lower lobe of lung	UBERON:0008949	60.04	silver quality
caput epididymis	UBERON:0004358	59.21	gold quality
body of pancreas	UBERON:0001150	59.13	gold quality
medulla oblongata	UBERON:0001896	58.19	gold quality
sural nerve	UBERON:0015488	57.76	gold quality
pons	UBERON:0000988	57.62	silver quality
upper leg skin	UBERON:0004262	57.60	gold quality
ventral tegmental area	UBERON:0002691	57.49	gold quality
cerebellar vermis	UBERON:0004720	56.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	56.21	silver quality
epithelial cell of pancreas	CL:0000083	55.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
lateral globus pallidus	UBERON:0002476	53.50	silver quality
pancreas	UBERON:0001264	52.92	gold quality
dorsal plus ventral thalamus	UBERON:0001897	52.57	gold quality
deltoid	UBERON:0001476	51.94	gold quality
seminal vesicle	UBERON:0000998	50.80	gold quality
myocardium	UBERON:0002349	50.25	gold quality
ectocervix	UBERON:0012249	49.99	gold quality
uterine cervix	UBERON:0000002	49.67	gold quality
colonic epithelium	UBERON:0000397	49.37	gold quality
buccal mucosa cell	CL:0002336	49.03	gold quality
bone marrow cell	CL:0002092	48.96	gold quality
substantia nigra pars compacta	UBERON:0001965	48.83	gold quality
prostate gland	UBERON:0002367	48.67	gold quality
cardia of stomach	UBERON:0001162	48.49	gold quality
ileal mucosa	UBERON:0000331	48.22	silver quality
quadriceps femoris	UBERON:0001377	47.75	gold quality
subthalamic nucleus	UBERON:0001906	47.45	silver quality
endocervix	UBERON:0000458	47.05	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	45.17	gold quality
spleen	UBERON:0002106	44.74	gold quality
medial globus pallidus	UBERON:0002477	44.64	silver quality
adult organism	UBERON:0007023	44.34	gold quality
rectum	UBERON:0001052	44.21	gold quality
monocyte	CL:0000576	44.11	gold quality
fallopian tube	UBERON:0003889	44.11	gold quality
right uterine tube	UBERON:0001302	44.01	silver quality
skin of hip	UBERON:0001554	44.01	silver quality
anatomical system	UBERON:0000467	43.95	gold quality
material anatomical entity	UBERON:0000465	43.92	gold quality
multicellular organism	UBERON:0000468	43.92	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
smooth muscle tissue	UBERON:0001135	43.49	gold quality
skeletal muscle tissue	UBERON:0001134	43.39	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	76.85
E-HCAD-25	yes	19.28
E-ANND-3	yes	8.52
E-ENAD-17	no	77.09

HPA expression

RNA tissue specificity: Tissue enhanced

44 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Amygdala	tissue	35.5
Olfactory bulb	tissue	25.2
Hippocampal formation	tissue	24.1
Cerebral cortex	tissue	23.9
Retrosplenial and cingulate cortex	tissue	23.9
Temporal cortex	tissue	23.9
Septum	tissue	23.8
Motor cortex	tissue	23.4
Insular cortex	tissue	23.1
Ventral forebrain	tissue	22.7
Retrosplenial cortex	tissue	22.1
Prefrontal cortex	tissue	21.9
Putamen	tissue	21.9
Basal ganglia	tissue	21.8
Entorhinal cortex	tissue	21.7
Somatosensory cortex	tissue	20.6
Occipital cortex	tissue	20.5
Hypothalamus	tissue	20.1
Midbrain	tissue	19.6
Hippocampus	tissue	19.5
Periaqueductal gray	tissue	18.9
Cerebellum	tissue	18.3
Pons	tissue	18.1
Postcentral gyrus	tissue	17.7
Thalamus	tissue	16.6
Nucleus accumbens	tissue	16.3
Superior colliculi	tissue	15.7
Substantia nigra	tissue	12.2
Medulla oblongata	tissue	11.1
Locus coeruleus	tissue	10.6
Spinal cord	tissue	9.2
Corpus callosum	tissue	5.8
Caudate putamen	tissue	5.7
Frontal cortex	tissue	3.2
Choroid plexus	tissue	1.6
Testis	tissue	0.9
Retina	tissue	0.6
Vagina	tissue	0.4
Spleen	tissue	0.3
Seminal vesicle	tissue	0.2
Prostate	tissue	0.2
Fallopian tube	tissue	0.2
Cervix	tissue	0.1
Pituitary gland	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Corticomedial amygdala (25.8), Posterior cingulate cortex (24.2), Subiculum (24.1), Dentate gyrus (23.6), Hippocampus, CA1 (23.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CSMD3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 213 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939

Functional genomics

gnomAD constraint: pLI 0.973, LOEUF 0.464, missense Z 2.24 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000297405 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:112,224,774–112,666,321	3255 / 3380.2	0.96	no
8:112,666,322–112,829,687	279 / 369.0	0.76	no
8:112,829,688–113,436,854	731 / 755.4	0.97	no

Literature-anchored findings (GeneRIF, showing 6)

• CSMD3 protein domain structure and the sequence of the cytoplasmic tail are highly conserved between mammals and fish. (PMID:12906867)
• CSMD3 encodes a protein with CUB and sushi multiple domains and is a candidate gene for benign adult familial myoclonic epilepsy on human chromosome 8q23.3-q24.1 (PMID:12943675)
• CSMD3 is deleted in a subject with combined tricho-rhino-phalangeal syndrome II with mental retardation and growth hormone deficiency. (PMID:15523607)
• Breakpoints on chromosomes 8 in both patients do not interrupt any known gene but both map in a region containing the CSMD3 gene, which thereby can be considered as a candidate for autistic spectrum disorders (PMID:18270536)
• Single-nucleotide polymorphisms in CSMD3 is associated with prostate cancer risk in hispanic men. (PMID:19528667)
• Nonsynonymous variants of CSMD3 is associated with familial colorectal cancer. (PMID:21351276)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	csmd3a	ENSDARG00000077905
danio_rerio	csmd3b	ENSDARG00000077920
mus_musculus	Csmd3	ENSMUSG00000022311
rattus_norvegicus	Csmd3	ENSRNOG00000004937

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2386403) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 35 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating HDL cholesterol level	1
abnormal coat/ hair morphology	1
abnormal spleen morphology	1
enlarged lymph nodes	1
abnormal cerebral cortex lamination	1
decreased body length	1
decreased body weight	1
abnormal social investigation	1
increased anxiety-related response	1
increased grooming behavior	1
abnormal object recognition memory	1
limb grasping	1
postnatal growth retardation	1
abnormal skin morphology	1
decreased brain weight	1
abnormal lymph node morphology	1
increased thigmotaxis	1
abnormal nervous system development	1
increased lean body mass	1
decreased neuronal precursor cell number	1
increased brain size	1
increased circulating bilirubin level	1
eye hemorrhage	1
thin cerebral cortex	1
abnormal neurite morphology	1

+10 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saguinus mystax	O19124	100.0%	Diamond
Saguinus oedipus	O62837	100.0%	Diamond
Gorilla gorilla gorilla	Q864V9	99.6%	Diamond
Pongo pygmaeus	Q8SQ75	99.6%	Diamond
Pan troglodytes	Q8SQ74	99.5%	Diamond
Pongo abelii	Q5RA73	99.2%	Diamond
Macaca fascicularis	Q9BE74	99.0%	Diamond
Oryctolagus cuniculus	P98065	93.5%	Diamond
Gallus gallus	P0DJJ2	93.2%	Diamond
Coturnix japonica	P42662	93.2%	Diamond
Saimiri sciureus	O62685	89.1%	Diamond
Gekko japonicus	A8WCC4	87.2%	Diamond
Bos taurus	P81187	85.9%	Diamond
Sus scrofa	Q03710	85.9%	Diamond
Equus caballus	Q95LG1	82.2%	Diamond
Caenorhabditis elegans	P98060	80.0%	Diamond
Xenopus laevis	Q90Y90	70.1%	Diamond
Drosophila melanogaster	Q0KHY3	59.0%	Diamond
Brugia malayi	D5FM38	51.2%	Diamond
Acropora millepora	B3EX01	49.0%	Diamond
Vaccinia virus WR	P68638	100.0%	Diamond
Vaccinia virus Copenhagen	P68639	100.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR2053	ncRNA	100302225
LINC02237	ncRNA	105375706

Protein

Protein identifiers

CUB and sushi domain-containing protein 3 — Q7Z407 (reviewed: Q7Z407)

Alternative names: CUB and sushi multiple domains protein 3

All UniProt accessions (2): H7BXX0, Q7Z407

UniProt curated annotations — full annotation on UniProt →

Function. Involved in dendrite development.

Subcellular location. Cell membrane.

Tissue specificity. Weakly expressed in most tissues, except in brain. Expressed at intermediate level in brain, including cerebellum, substantia nigra, thalamus, spinal cord, hippocampus and fetal brain. Also expressed in testis.

Domain organisation. The intracellular region is dispensable for its function.

Similarity. Belongs to the CSMD family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q7Z407-1	1	yes
Q7Z407-2	2
Q7Z407-3	3
Q7Z407-4	4
Q7Z407-5	5

RefSeq proteins (4): NP_001350114, NP_443132, NP_937756, NP_937757 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR000859	CUB_dom	Domain
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR051277	SEZ6_CSMD_C4BPB_Regulators	Family

Pfam: PF00084, PF00431

UniProt features (179 total): disulfide bond 70, domain 42, glycosylation site 41, sequence variant 7, splice variant 6, sequence conflict 4, topological domain 3, transmembrane region 2, region of interest 2, chain 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

No AlphaFold model available for Q7Z407 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Human Protein Atlas

Protein class: Predicted membrane proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH uncertain · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (70)

Type

Positions

Disulfide bond

690–717, 721–747, 834–875, 860–891, 895–921, 1010–1050, 1036–1063, 1067–1093, 1182–1222, 1208–1237, 1241–1267, 1354–1395, 1381–1410, 1414–1441, 1528–1568, 1554–1584, 1588–1614, 1701–1741, 1727–1758, 1762–1788, 1878–1918, 1904–1935, 1939–1965, 2052–2092, 2078–2107, 2111–2137, 2224–2264, 2250–2279, 2283–2309, 2395–2437, 2423–2452, 2456–2484, 2569–2610, 2596–2627, 2632–2674, 2658–2689, 2694–2739, 2725–2754, 2759–2799, 2785–2812 … (+30)

Glycosylation sites (41)

Type	Positions
N-linked (glcnac…) asparagine	73, 90, 361, 409, 724, 823, 966, 1092, 1126, 1171, 1280, 1536, 1591, 1709, 1781, 1929, 2019, 2155, 2286, 2291, 2324, 2495, 2537, 2711, 2742, 2862, 2932, 2952, 3099, 3158, 3167, 3194, 3208, 3218, 3276, 3364, 3522, 3529, 3612, 3618 … (+1)

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 200 (showing top): GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, RRAGTTGT_UNKNOWN, AP1_01, BENPORATH_ES_WITH_H3K27ME3, GCANCTGNY_MYOD_Q6, AREB6_01, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, FOXO4_01, CAGCTG_AP4_Q5, ATGTTAA_MIR302C, EVI1_05, CCANNAGRKGGC_UNKNOWN, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (1): regulation of dendrite development (GO:0050773)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

6 GO namespaces:

Category	Terms
regulation of neuron projection development	1
dendrite development	1
regulation of developmental process	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 1,074 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSMD3	ANXA13	P27216	841
CSMD3	TRPS1	Q9UHF7	827
CSMD3	MUC16	Q8WXI7	775
CSMD3	LRP1B	Q9NZR2	775
CSMD3	TTN	Q8WZ42	761
CSMD3	ZFHX4	Q86UP3	741
CSMD3	EXT1	Q16394	718
CSMD3	USH2A	O75445	716
CSMD3	SYNE1	Q8NF91	716
CSMD3	PCLO	Q9Y6V0	716
CSMD3	FAT3	Q8TDW7	715
CSMD3	RYR2	Q92736	702
CSMD3	XIRP2	A4UGR9	701
CSMD3	TP53	P04637	621
CSMD3	GDF6	Q6KF10	617

IntAct

BioGRID (6 interactions; top human partners by supporting records): EGFR (Positive Genetic), NEK4 (Affinity Capture-MS), NUP43 (Proximity Label-MS)

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 18 cancer types — BLCA, BRCA, COAD, COADREAD, ESCA, GBM, HCC, HNSC, LUAD, LUSC, MEL, OVT…(+6 more).

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for CSMD3: 580 ClinVar records (0 pathogenic / likely pathogenic); 21 GWAS associations.

ClinVar

580 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	459
Likely benign	47
Benign	42

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 8,226):

Position(s)	Effect	Δscore	Sites
8:112231543–112231544	donor_loss	1.0000	6
8:112231633–112231634	acceptor_loss	1.0000	3
8:112234363–112234364	donor_loss	1.0000	4
8:112234478–112234479	acceptor_loss	1.0000	6
8:112237188–112237189	donor_loss	1.0000	4
8:112241726	donor_gain	1.0000
8:112244574–112244575	acceptor_loss	1.0000	6
8:112244576	acceptor_gain	1.0000
8:112247018–112247019	donor_loss	1.0000	5
8:112265596	acceptor_gain	1.0000

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 24,333 scored), across 1,484 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D1991	8	0.999	1.000
D2335	8	0.999	1.000
D2163	8	0.998	1.000
D1640	8	0.997	0.999
D2376	8	0.996	0.999
D2204	8	0.995	0.999
D2032	8	0.993	0.999
D1681	8	0.992	0.998
D2510	8	0.992	0.998
F2383	8	0.990	0.999
F3495	8	0.988	0.999
F1984	8	0.987	0.999
D1997	8	0.987	0.998
F2325	8	0.986	0.998
F2373	8	0.983	1.000
D1813	8	0.982	0.996
D2341	8	0.981	0.998
F2560	8	0.981	0.999
F1516	8	0.976	0.998
F1678	8	0.975	0.998

HPA cancer prognostics

RNA cancer specificity: Not detected

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	5.38e-05

Disease associations

OMIM: gene MIM:608399 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

GWAS associations

21 associations:

Study	Trait	p-value
GCST007324_1	Adventurousness	8e-13
GCST003123_20	Severe influenza A (H1N1) infection	6e-11
GCST006959_85	Rheumatoid arthritis	7e-10
GCST006606_1	Response to TNF inhibitor in rheumatoid arthritis (change in swollen 28-joint count)	2e-8
GCST006959_88	Rheumatoid arthritis	5e-8
GCST002941_4	Airway imaging phenotypes	3e-7
GCST003901_2	Cognitive decline (age-related)	3e-7
GCST007277_12	Tourette syndrome	6e-7
GCST002826_13	Urate levels (BMI interaction)	7e-7
GCST012300_3	Schizophrenia, bipolar disorder or major depressive disorder	9e-7
GCST001531_13	Temperament	2e-6
GCST001588_4	Periodontal microbiota	2e-6
GCST002783_554	Body mass index	2e-6
GCST009391_1682	Metabolite levels	2e-6
GCST003154_3	Peripheral artery disease	3e-6
GCST003831_24	Asthma	3e-6
GCST009391_1683	Metabolite levels	3e-6
GCST012297_8	Schizophrenia, bipolar disorder or major depressive disorder	3e-6
GCST002104_23	Bronchopulmonary dysplasia	6e-6
GCST005790_62	Rosacea symptom severity	7e-6
GCST006606_13	Response to TNF inhibitor in rheumatoid arthritis (change in swollen 28-joint count)	8e-6

EFO canonical traits (from GWAS)

10 canonical traits:

EFO ID	Trait name
EFO:0004825	temperament and character inventory
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0007627	airway imaging measurement
EFO:1001488	influenza A (H1N1)
EFO:0009180	rosacea severity measurement
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0008579	risk-taking behaviour
EFO:0005058	tyrosine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation, increases mutagenesis	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Valproic Acid	affects expression, decreases methylation	2
bisphenol A	affects cotreatment, decreases methylation	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Allergens	increases expression	1
Arsenic	affects methylation	1
Methapyrilene	decreases methylation	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9T20	OV-4453	Cancer cell line	Female
CVCL_A1SN	TOV-3121EP	Cancer cell line	Female
CVCL_A7NI	2XSB	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 211 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT04081701	Phase 4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT04386642	Phase 4	UNKNOWN	Tranexamic Acid Reduce Blood Loss in Meningioma Resection
NCT06377371	Phase 4	RECRUITING	Feasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00517959	Phase 3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01655927	Phase 3	UNKNOWN	Efficacy of Tranexamic Acid in Brain Tumor Resections
NCT03015701	Phase 3	COMPLETED	S9005 Mifepristone in Meningioma
NCT03558516	Phase 3	COMPLETED	Magnesium and Intraoperative Blood Loss in Meningioma Surgery
NCT04305470	Phase 3	COMPLETED	Gleolan for Visualization of Newly Diagnosed or Recurrent Meningioma
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00003483	Phase 2	TERMINATED	Antineoplaston Therapy in Treating Patients With Meningioma
NCT00589784	Phase 2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00706810	Phase 2	COMPLETED	Combination of Hydroxyurea and Verapamil for Refractory Meningiomas
NCT00859040	Phase 2	COMPLETED	Monthly SOM230C for Recurrent or Progressive Meningioma
NCT01967823	Phase 2	COMPLETED	T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
NCT02523014	Phase 2	RECRUITING	Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
NCT02648997	Phase 2	ACTIVE_NOT_RECRUITING	An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma
NCT02831257	Phase 2	COMPLETED	AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas
NCT02847559	Phase 2	COMPLETED	Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma
NCT03013387	Phase 2	WITHDRAWN	Dosimetry Guided PRRT With 90Y-DOTATOC
NCT03071874	Phase 2	ACTIVE_NOT_RECRUITING	Vistusertib (AZD2014) For Recurrent Grade II-III Meningiomas
NCT03095248	Phase 2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03273712	Phase 2	COMPLETED	Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)
NCT03971461	Phase 2	ACTIVE_NOT_RECRUITING	Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
NCT04082520	Phase 2	RECRUITING	Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy
NCT04298541	Phase 2	WITHDRAWN	Direct Comparison of Ga-68-DOTATATE and Ga-68-DOTATOC
NCT04374305	Phase 2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04659811	Phase 2	ACTIVE_NOT_RECRUITING	Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma
NCT05425004	Phase 2	RECRUITING	Cabozantinib for Patients With Recurrent or Progressive Meningioma
NCT05940493	Phase 2	RECRUITING	Abemaciclib in Newly Diagnosed Meningioma Patients
NCT06012929	Phase 2	WITHDRAWN	A Study of ONC201 for Refractory Meningioma
NCT06126588	Phase 2	RECRUITING	Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
NCT06132685	Phase 2	RECRUITING	Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial
NCT06322342	Phase 2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT06326190	Phase 2	RECRUITING	177Lu-DOTATATE for Recurrent Meningioma
NCT06439420	Phase 2	COMPLETED	CBT-I in Primary Brain Tumor Patients: Phase IIc Randomized Feasibility Pilot Trial
NCT06684795	Phase 2	UNKNOWN	FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery
NCT06710249	Phase 2	RECRUITING	Impact of Salovum® and SPC® Flakes on Brain Tumor Induced Edema
NCT06804655	Phase 2	RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07428616	Phase 2	RECRUITING	A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma
NCT07533942	Phase 2	RECRUITING	A Study of JZP3507 (ONC206) in Recurrent Grade 2 or 3 Meningioma
NCT07707947	Phase 2	NOT_YET_RECRUITING	Selumetinib for NF2-Related Schwannomatosis
NCT07713745	Phase 2	NOT_YET_RECRUITING	Platform Research for Innovative Medicines in NF2-SWN (PRIME-NF2)
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT03267836	Phase 1	TERMINATED	Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma