CSMD1

Summary

CSMD1 (CUB and Sushi multiple domains 1, HGNC:14026) is a protein-coding gene on chromosome 8p23.2, encoding CUB and sushi domain-containing protein 1 (Q96PZ7). Potential suppressor of squamous cell carcinomas.

Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be located in membrane.

Source: NCBI Gene 64478 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism spectrum disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 121
• Clinical variants (ClinVar): 1,150 total — 1 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 2
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_033225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14026
Approved symbol	CSMD1
Name	CUB and Sushi multiple domains 1
Location	8p23.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1890, PPP1R24
Ensembl gene	ENSG00000183117
Ensembl biotype	protein_coding
OMIM	608397
Entrez	64478

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding_CDS_not_defined, 6 protein_coding, 2 retained_intron

ENST00000335551, ENST00000400186, ENST00000518151, ENST00000519090, ENST00000519623, ENST00000520002, ENST00000520451, ENST00000520561, ENST00000520630, ENST00000521646, ENST00000523062, ENST00000523387, ENST00000523488, ENST00000524177, ENST00000602557, ENST00000602723, ENST00000635120

RefSeq mRNA: 1 — MANE Select: NM_033225 NM_033225

CCDS: CCDS55189

Canonical transcript exons

ENST00000635120 — 70 exons

Exon	Start	End
ENSE00001337196	3096849	3097037
ENSE00001337303	3396194	3396381
ENSE00001337308	3406027	3406221
ENSE00001337309	3407899	3408225
ENSE00001390107	2954224	2954268
ENSE00001541896	3997903	3998110
ENSE00001541898	4031905	4032099
ENSE00001593866	3616710	3616797
ENSE00001604504	3106528	3106641
ENSE00001610794	2998011	2998184
ENSE00001618094	3108603	3108748
ENSE00001632174	2973117	2973299
ENSE00001634359	2955589	2955768
ENSE00001639117	3708414	3708491
ENSE00001642699	3574945	3575066
ENSE00001645867	3052462	3052647
ENSE00001646384	2966570	2966746
ENSE00001647726	3118399	3118587
ENSE00001653652	2963222	2963395
ENSE00001660352	3399391	3399529
ENSE00001666981	2978612	2978800
ENSE00001697137	2949299	2949386
ENSE00001705572	2950231	2950343
ENSE00001716902	2957696	2957807
ENSE00001719912	2974451	2974624
ENSE00001724024	3091516	3091662
ENSE00001725197	3110158	3110335
ENSE00001736687	3409423	3409605
ENSE00001741713	3107718	3107798
ENSE00001752958	2962466	2962639
ENSE00001753984	2942472	2942604
ENSE00001754635	2951114	2951275
ENSE00001760704	2961141	2961214
ENSE00001774787	2999958	3000131
ENSE00001778596	3087097	3087285
ENSE00001790731	2965775	2965954
ENSE00002097594	4637342	4637558
ENSE00002110069	3586136	3586260
ENSE00002122291	3753930	3754042
ENSE00002125828	4419953	4420065
ENSE00003463123	3188887	3189011
ENSE00003486173	3181110	3181214
ENSE00003488848	3201612	3201725
ENSE00003492107	3230040	3230231
ENSE00003500203	3157897	3157966
ENSE00003500741	3029319	3029513
ENSE00003517944	3219255	3219442
ENSE00003532075	3214497	3214691
ENSE00003534953	3162159	3162277
ENSE00003543605	3199714	3199809
ENSE00003554364	3347992	3348161
ENSE00003566862	3142465	3142674
ENSE00003571994	3187869	3187965
ENSE00003573928	3367032	3367247
ENSE00003582999	3151397	3151513
ENSE00003589893	3018477	3018650
ENSE00003608110	3308312	3308503
ENSE00003609504	3468712	3468824
ENSE00003616600	3493623	3493726
ENSE00003634507	3369254	3369370
ENSE00003644099	3387494	3387682
ENSE00003645505	3284144	3284346
ENSE00003651393	3189912	3190115
ENSE00003656117	3307695	3307821
ENSE00003656592	3205504	3205620
ENSE00003657161	3359152	3359340
ENSE00003657934	3223729	3223867
ENSE00003660564	3343294	3343450
ENSE00003845808	4994332	4994914
ENSE00003850716	2935361	2938744

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 97.42.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7782 / max 287.4971, expressed in 270 samples.

FANTOM5 promoters (28 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91662	1.7832	121
91667	0.5097	86
91664	0.4372	85
91638	0.4090	89
91659	0.3861	83
91665	0.3792	81
91660	0.1905	63
91656	0.0871	51
91613	0.0623	16
91661	0.0608	31

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	97.42	gold quality
middle temporal gyrus	UBERON:0002771	94.02	gold quality
primary visual cortex	UBERON:0002436	89.13	gold quality
entorhinal cortex	UBERON:0002728	87.91	gold quality
superior frontal gyrus	UBERON:0002661	87.82	gold quality
postcentral gyrus	UBERON:0002581	87.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.26	gold quality
endothelial cell	CL:0000115	87.08	silver quality
occipital lobe	UBERON:0002021	86.25	gold quality
buccal mucosa cell	CL:0002336	86.21	gold quality
parietal lobe	UBERON:0001872	86.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.09	gold quality
frontal cortex	UBERON:0001870	80.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.30	gold quality
cerebral cortex	UBERON:0000956	79.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.73	gold quality
neocortex	UBERON:0001950	79.64	gold quality
prefrontal cortex	UBERON:0000451	79.43	gold quality
temporal lobe	UBERON:0001871	78.83	gold quality
corpus callosum	UBERON:0002336	78.61	gold quality
right frontal lobe	UBERON:0002810	78.06	gold quality
Ammon’s horn	UBERON:0001954	77.55	gold quality
anterior cingulate cortex	UBERON:0009835	76.59	gold quality
oocyte	CL:0000023	76.55	silver quality
cortical plate	UBERON:0005343	76.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.89	gold quality
spinal cord	UBERON:0002240	74.17	gold quality
forebrain	UBERON:0001890	74.00	gold quality
brain	UBERON:0000955	73.20	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	12215.81
E-HCAD-35	yes	92.99
E-HCAD-25	yes	75.17
E-ANND-3	yes	8.47
E-GEOD-99795	no	141.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

214 targeting CSMD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
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
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

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Simple inactivation of CSMD1 may not explain the deletions observed in oropharyngeal squamous cell carcinoma and may call into question the role of this gene in head and neck carcinogenesis. (PMID:12696061)
• CSMD1 is a member of a suite of genes whose downregulation is predictive of prostate cancer relapse (PMID:12874026)
• CSMD1 protein domain structure and the sequence of the cytoplasmic tail are highly conserved between mammals and fish (PMID:12906867)
• Previously reported apparent homozygous deletions wholly contained within CSMD1 introns are a PCR artifact caused by SNPs within the primer sequences. The allele remaining after LOH can’t be amplified by these primers. (PMID:14506705)
• CSMD1 expression is markedly decreased in high stage prostatic adenocarcinomas (PMID:15138198)
• CSMD1 expression is aberrant in most SCC cell lines. Reduced expression is associated with methylation of a specific region of the promoter. Other defects include loss of specific exons during splicing and activation of cryptic promoters. (PMID:16153303)
• BAC microarray-CGH detects homozygous deletion of CSMD1 in human bladder cancer specimens (PMID:16203795)
• CSMD1 is located within fragile site FRA8B. (PMID:16221525)
• The region around CSMD1 has the highest sequence diversity between humans and the highest sequence divergance between humans and chimps in the genome. (PMID:16421571)
• CSMD1 protein blocks activation of the classical complement pathway (PMID:16547280)
• CSMD1 mutations may play a role in the development of colorectal cancer. (PMID:18614856)
• Characterization of CSMD1 in a large set of primary lung, head and neck, breast, and skin cancer tissues is reported. (PMID:19276661)
• Reduction of CSMD1 expression significantly associated with high tumour grade and decreased overall survival in invasive ductal breast carcinoma (PMID:19669408)
• Consistent genetic factors for ATP2B1, CSK, ARSG and CSMD1 were present, which have been shown to be associated with high blood pressure and hypertension in two Korean cohorts. (PMID:19960030)
• data demonstrate a significant role of complement control-related genes in the etiology of schizophrenia. (PMID:21439553)
• results confirm the role of CSDM1 as a tumor suppressor gene in melanoma cells; study also found that CSMD1 can interact with Smad3, activate Smad1, Smad2, and Smad3, and increase the expression of Smad4 (PMID:22538441)
• CSMD1 schizophrenia risk ‘A’ allele at rs10503253 is associated with impaired cognition and memory function, but not attentinal control. (PMID:23320435)
• CSMD1 alterations can correlate with earlier clinical presentation in colorectal tumors, thus further implicating CSMD1 as a tumor suppressor gene. (PMID:23505554)
• TNIP1/ANXA6 and CSMD1 variants interacting with cigarette smoking and alcohol intake affect risk of psoriasis. (PMID:23541940)
• Single nucleotide polymorphism rs10503253 within the CSMD1 gene is associated with cognition disorder in schizophrenia. (PMID:23839771)
• CSMD1 inhibits complement by promoting factor I-mediated C4b/C3b degradation and inhibition of membrane attack complex assembly. (PMID:23964079)
• role of CSMD1 and SYNE1 in the etiology of bipolar disorder (PMID:24387768)
• CSMD1 and CSMD2 expressions were associated with overall survival (PMID:24408017)
• Results underline the relevance of the risk “A” allele to neurocognitive functioning and suggest that its detrimental effects on cognition, may be part of the mechanism by which the CSMD1 mediates risk for schizophrenia (PMID:24630139)
• A SNP within CSMD1 associated with variation in the potential osteoarthritis biomarker uCTX-II levels with borderline genome-wide significance. (PMID:25057126)
• This exploratory study reports two plausible loci associated with systolic blood pressure response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of alphaENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case-control study. (PMID:25695618)
• The associations of rs2616984 in CSMD1 gene, putative associations of rs3131296 in NOTCH4 gene, and associations of rs2229741 of NRIP1 gene with Alzheimer’s disease have been found in a Russian population. (PMID:25845235)
• Loss of heterozygosity at D8S262 and down-regulation of CSMD1 expression may be early events in hepatocarcinogenesis. (PMID:26076954)
• In the first published genome-wide association study of postburn hypertrophic scarring (HTS), we report that a common intronic variant in the CSMD1 gene is associated with reduced severity of postburn HTS. (PMID:26366535)
• Allele-wise association analysis detected three SNPs, including rs2623659 in the CUB and Sushi multiple domains-1 (CSMD1) gene, associated with severity of illness at end point. The severity of illness at end point was associated with treatment response, but not with the severity of illness at baseline. Three SNPs, including rs2294424 in the C6orf105 gene, were associated with social outcomes. (PMID:26674612)
• This study failed to observe any association between rs12861349 and parkinson disear in iran population. (PMID:26732583)
• findings do not support an association between CSMD1 rs10503253 and Schizophrenia in a Han Chinese population. (PMID:27377754)
• CSMD1 gene is a target for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma. (PMID:27636103)
• Data show that micrRNA miR-10b is overexpressed in hepatocellular carcinoma (HCC) tissues and miR-10b mimics promoted HCC cell viability and invasion via targeting CUB and Sushi multiple domains 1 (CSMD1) expression. (PMID:27756250)
• Study provide experimental evidence for the role of CSMD1 as a tumor suppressor in vitro and in vivo in the progression of breast cancer. Results revealed that expression of CSMD1 significantly reduced cell motility and migration, adhesion and invasion, as well as the tumorigenic and signaling potential of human breast cancer cells. (PMID:27764775)
• we studied n=3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. (PMID:27890662)
• rs10503253 is likely a common schizophrenia risk variant in multiple ethnic groups (PMID:28344127)
• Low expression of CSMD1 is associated with enhanced proliferation, migration and invasion. (PMID:28534981)
• We show that the gene body of an autosomal gene, CSMD1, is differentially methylated in a sex- and placental-specific manner, displaying sex-specific differences in placental transcript abundance (PMID:29376485)
• CSMD1-related gene signatures are associated with the prognosis of HNSCC patients. (PMID:30545040)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Csmd1	ENSMUSG00000060924
rattus_norvegicus	Csmd1	ENSRNOG00000030719

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), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

CUB and sushi domain-containing protein 1 — Q96PZ7 (reviewed: Q96PZ7)

Alternative names: CUB and sushi multiple domains protein 1

All UniProt accessions (4): Q96PZ7, E5RIG2, F8W9C3, H7BXU2

UniProt curated annotations — full annotation on UniProt →

Function. Potential suppressor of squamous cell carcinomas.

Subcellular location. Membrane.

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

Miscellaneous. CSMD1 may be a candidate for oral and oropharyngeal squamous cell carcinomas (OSCCs). PubMed:12696061 and PubMed:14506705 are however in disagreement: while PubMed:14506705 considers CSMD1 as a strong candidate for OSCCs, PubMed:12696061 thinks it is not.

Similarity. Belongs to the CSMD family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96PZ7-1	1	yes
Q96PZ7-2	2, Short
Q96PZ7-3	3
Q96PZ7-4	4

RefSeq proteins (1): NP_150094* (*=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 (183 total): disulfide bond 70, domain 42, glycosylation site 40, sequence conflict 10, splice variant 6, sequence variant 6, strand 4, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EHF	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q96PZ7 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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): 873–913, 899–926, 930–956, 1045–1085, 1071–1100, 1104–1130, 1217–1258, 1244–1273, 1277–1304, 1391–1431, 1417–1447, 1451–1477, 1564–1604, 1590–1621, 1625–1651, 1741–1781, 1767–1798, 1802–1828, 1915–1955, 1941–1970 …

Glycosylation sites (40): 40, 57, 587, 686, 955, 1015, 1034, 1184, 1197, 1399, 1454, 1572, 1644, 1792, 1805, 1882, 2018, 2149, 2154, 2187 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_MEMORY, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_GLAND_MORPHOGENESIS, GOBP_BEHAVIOR, ATACCTC_MIR202, GOBP_ASSOCIATIVE_LEARNING, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, GOBP_STARTLE_RESPONSE, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_LEARNING

GO Biological Process (11): startle response (GO:0001964), memory (GO:0007613), male gonad development (GO:0008584), female gonad development (GO:0008585), gene expression (GO:0010467), oviduct epithelium development (GO:0035846), glucose homeostasis (GO:0042593), mammary gland branching involved in pregnancy (GO:0060745), conditioned place preference (GO:1990708), mammary gland development (GO:0030879), mammary gland duct morphogenesis (GO:0060603)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gonad development	2
developmental process involved in reproduction	2
response to external stimulus	1
neuromuscular process	1
learning or memory	1
development of primary male sexual characteristics	1
development of primary female sexual characteristics	1
macromolecule biosynthetic process	1
oviduct development	1
epithelium development	1
carbohydrate homeostasis	1
maternal process involved in female pregnancy	1
branching involved in mammary gland duct morphogenesis	1
associative learning	1
gland development	1
mammary gland morphogenesis	1
epithelial tube morphogenesis	1
mammary gland epithelium development	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSMD1	WBP1L	Q9NX94	666
CSMD1	SLC35F2	Q8IXU6	616
CSMD1	ZNF804A	Q7Z570	607
CSMD1	LRP1B	Q9NZR2	576
CSMD1	NT5C2	P49902	568
CSMD1	SERPINB8	P50452	535
CSMD1	CACNA1C	Q13936	531
CSMD1	DOP1B	Q9Y3R5	531
CSMD1	PTPRD	P23468	529
CSMD1	TENM4	Q6N022	527
CSMD1	MCPH1	Q8NEM0	515
CSMD1	PTPRT	O14522	507
CSMD1	PCLO	Q9Y6V0	481
CSMD1	NAALADL2	Q58DX5	472
CSMD1	GRIK2	Q13002	471

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CSMD1	SMAD3	psi-mi:“MI:0403”(colocalization)	0.560
CSMD1	SMAD3	psi-mi:“MI:0915”(physical association)	0.560
CSMD1	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
CSMD1	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.400
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350
AKR1B1	CSMD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): CSMD1 (Affinity Capture-RNA), CSMD1 (Affinity Capture-RNA), CSMD1 (Proximity Label-MS), CSMD1 (Affinity Capture-MS), CSMD1 (Positive Genetic), CSMD1 (Affinity Capture-MS), CSMD1 (Affinity Capture-RNA), CSMD1 (Affinity Capture-MS), CSMD1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1D5NSM8, A2AVA0, B8JI71, D3ZHH1, F1RWC3, O57409, O60494, O70244, O75445, P0C6B8, P25723, P35442, P56677, P82279, P86091, P97435, P98072, P98073, P98074, P98160, Q05793, Q0IIH7, Q16787, Q20176, Q2QI47, Q4LDE5, Q5ZQU0, Q61789, Q66TN7, Q70E20, Q7RTY8, Q7RTZ1, Q7Z407, Q7Z408, Q80T79, Q8BIK6, Q8K3K1, Q8K480, Q8UWJ4, Q8VHS2

Diamond homologs: A0JNA2, B3EWZ7, B3EX01, F1RWC3, O60494, O70244, P56677, Q0IIH7, Q4A3R3, Q53EL9, Q5VXM1, Q60997, Q7TSK2, Q7Z407, Q7Z408, Q80T79, Q8BQH6, Q8BZE1, Q8CIZ5, Q8R4W6, Q923L3, Q95218, Q96PZ7, Q9JLB4, Q9TU53, Q9UGM3, Q9UKZ9, Q9W332, Q9Y5Y6, A8Q2D1, C6K2K4, C6KFA3, D5FM38, O43897, O57460, P48740, P79953, P97435, P98064, Q5E9P5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CSMD1	“down-regulates quantity”	C3	binding
CSMD1	“down-regulates quantity”	C4B	binding
CSMD1	down-regulates	Angiogenesis
CSMD1	“up-regulates activity”	SMAD3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

1150 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	9
Uncertain significance	869
Likely benign	123
Benign	81

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
4819123	NM_033225.6(CSMD1):c.956C>G (p.Ser319Ter)	Pathogenic
155023	GRCh38/hg38 8p23.2(chr8:3934205-4230645)x1	Likely pathogenic
2635629	NM_033225.6(CSMD1):c.2729C>G (p.Pro910Arg)	Likely pathogenic
545355	NC_000008.11:g.(?2724493)(4921893_?)del	Likely pathogenic
545356	NC_000008.11:g.(?3873130)(3959547_?)del	Likely pathogenic
545357	NC_000008.11:g.(?3876145)(3961401_?)del	Likely pathogenic
545358	NC_000008.11:g.(?3876145)(3967152_?)del	Likely pathogenic
545359	NC_000008.11:g.(?3877806)(3959547_?)del	Likely pathogenic
545360	NC_000008.11:g.(?3914469)(4157437_?)del	Likely pathogenic
545361	NC_000008.11:g.(?4410048)(4458635_?)del	Likely pathogenic

SpliceAI

14555 predictions. Top by Δscore:

Variant	Effect	Δscore
8:2938741:CGTT:C	acceptor_gain	1.0000
8:2938745:C:CC	acceptor_gain	1.0000
8:2949294:CTTA:C	donor_loss	1.0000
8:2949295:TTA:T	donor_loss	1.0000
8:2949296:TA:T	donor_loss	1.0000
8:2949297:A:AT	donor_loss	1.0000
8:2949298:C:CT	donor_loss	1.0000
8:2949384:CAC:C	acceptor_gain	1.0000
8:2949385:AC:A	acceptor_gain	1.0000
8:2949385:ACC:A	acceptor_loss	1.0000
8:2949386:CC:C	acceptor_gain	1.0000
8:2949388:T:G	acceptor_loss	1.0000
8:2949391:C:CT	acceptor_gain	1.0000
8:2949393:C:CT	acceptor_gain	1.0000
8:2949394:A:AC	acceptor_gain	1.0000
8:2949394:A:C	acceptor_gain	1.0000
8:2951109:CCTA:C	donor_loss	1.0000
8:2951110:CTAC:C	donor_loss	1.0000
8:2951111:TA:T	donor_loss	1.0000
8:2951112:A:T	donor_loss	1.0000
8:2951113:CCTG:C	donor_loss	1.0000
8:2951272:GGAA:G	acceptor_gain	1.0000
8:2951273:GAA:G	acceptor_gain	1.0000
8:2951275:AC:A	acceptor_loss	1.0000
8:2951276:C:A	acceptor_loss	1.0000
8:2951276:C:CC	acceptor_gain	1.0000
8:2954267:ACCTA:A	acceptor_loss	1.0000
8:2954269:C:A	acceptor_loss	1.0000
8:2954270:T:G	acceptor_loss	1.0000
8:2955587:A:AC	donor_gain	1.0000

AlphaMissense

23454 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:2955614:C:A	W3323C	1.000
8:2955614:C:G	W3323C	1.000
8:2955616:A:G	W3323R	1.000
8:2955616:A:T	W3323R	1.000
8:2999983:C:A	W2726C	1.000
8:2999983:C:G	W2726C	1.000
8:3118424:C:A	W2135C	1.000
8:3118424:C:G	W2135C	1.000
8:3157922:C:A	W1963C	1.000
8:3157922:C:G	W1963C	1.000
8:3157924:A:G	W1963R	1.000
8:3157924:A:T	W1963R	1.000
8:3181121:A:G	L1905P	1.000
8:3189937:C:A	W1791C	1.000
8:3189937:C:G	W1791C	1.000
8:2942514:G:T	A3498D	0.999
8:2942523:G:C	P3495R	0.999
8:2942523:G:T	P3495H	0.999
8:2955594:C:G	C3330S	0.999
8:2955595:A:T	C3330S	0.999
8:2955679:A:G	C3302R	0.999
8:2957721:C:A	W3263C	0.999
8:2957721:C:G	W3263C	0.999
8:2957723:A:G	W3263R	0.999
8:2957723:A:T	W3263R	0.999
8:2966595:C:A	W3025C	0.999
8:2966595:C:G	W3025C	0.999
8:2998036:C:A	W2784C	0.999
8:2998036:C:G	W2784C	0.999
8:2998038:A:G	W2784R	0.999

dbSNP variants (sampled 300 via entrez): RS1000001014 (8:3956091 C>T), RS1000001928 (8:4192838 C>T), RS1000002423 (8:4638705 C>T), RS1000002631 (8:4516885 AAATAT>A), RS1000002841 (8:3153364 G>A,C), RS1000002877 (8:3232142 T>A), RS1000004950 (8:3899328 G>C), RS1000005279 (8:4305235 T>C), RS1000005489 (8:4176455 T>A,C,G), RS1000006962 (8:3337552 T>A,C), RS1000007220 (8:4400222 T>C), RS1000008376 (8:3487090 C>G,T), RS1000008501 (8:2991273 T>C,G), RS1000009253 (8:3768767 C>G), RS1000009679 (8:3826046 G>C)

Disease associations

OMIM: gene MIM:608397 | disease phenotypes: MIM:181500, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
autism spectrum disorder	Limited	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (5): autism spectrum disorder (MONDO:0005258), schizophrenia (MONDO:0005090), autism (MONDO:0005260), cerebellar ataxia (MONDO:0000437), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (3): Rare ataxia (Orphanet:102002), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia
HP:0000717	Autism

GWAS associations

121 associations (top):

Study	Trait	p-value
GCST000269_5	Multiple sclerosis	2.000000e-06
GCST000770_3	Emphysema-related traits	5.000000e-07
GCST000974_3	HDL cholesterol	6.000000e-06
GCST001208_7	Insulin resistance/response	8.000000e-06
GCST001242_11	Schizophrenia	2.000000e-08
GCST001444_2	Pulmonary function decline	9.000000e-06
GCST001491_29	Immune response to smallpox vaccine (IL-6)	5.000000e-07
GCST001565_14	Schizophrenia	9.000000e-07
GCST001762_270	Obesity-related traits	7.000000e-07
GCST001762_420	Obesity-related traits	7.000000e-06
GCST001762_515	Obesity-related traits	7.000000e-06
GCST001877_32	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	4.000000e-08
GCST001894_11	Endometriosis	6.000000e-06
GCST001915_22	Alzheimer’s disease (cognitive decline)	8.000000e-07
GCST001959_8	Eating disorders (purging via substances)	6.000000e-06
GCST002004_9	Adverse response to chemotherapy (neutropenia/leucopenia) (carboplatin)	7.000000e-06
GCST002028_2	Serum selenium levels	3.000000e-06
GCST002126_1	Periodontitis (CDC/AAP)	9.000000e-06
GCST002126_27	Periodontitis (CDC/AAP)	3.000000e-06
GCST002133_10	Illicit drug use	6.000000e-06
GCST002138_2	Waist-hip ratio	3.000000e-06
GCST002187_7	Systolic blood pressure in sickle cell anemia	8.000000e-06
GCST002249_1	Blood pressure measurement (high sodium intervention)	6.000000e-07
GCST002249_3	Blood pressure measurement (high sodium intervention)	3.000000e-07
GCST002254_5	Schizophrenia, schizoaffective disorder or bipolar disorder	5.000000e-08
GCST002337_64	Amyotrophic lateral sclerosis (sporadic)	2.000000e-07
GCST002408_4	Response to methotrexate in juvenile idiopathic arthritis	1.000000e-06
GCST002450_5	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	2.000000e-06
GCST002539_71	Schizophrenia	1.000000e-08
GCST002540_5	Osteoarthritis biomarkers	8.000000e-08

EFO canonical traits (57, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004713	FEV/FVC ratio
EFO:0004645	response to vaccine
EFO:0003940	physical activity
EFO:0004578	homocysteine measurement
EFO:0005431	illegal drug consumption
EFO:0004343	waist-hip ratio
EFO:0006335	systolic blood pressure
EFO:0005401	response to high sodium diet
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0005890	osteoarthritis biomarker measurement
EFO:0004703	age at menarche
EFO:0006798	neuritic plaque measurement
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:0006897	airway responsiveness measurement
EFO:0006995	response to diisocyanate
EFO:0007628	gas trapping measurement
EFO:0007626	emphysema imaging measurement
EFO:0006952	cytotoxicity measurement
EFO:0007747	postburn hypertrophic scarring severity measurement
EFO:0008457	cannabis dependence measurement
EFO:0007827	nighttime rest measurement
EFO:0007865	loneliness measurement
EFO:0007874	gut microbiome measurement
EFO:0007922	response to sulfonylurea
EFO:0007998	cognitive impairment measurement
EFO:0006941	grip strength measurement
EFO:0008337	psychosis predisposition measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11993031	Efficacy	3	hydrochlorothiazide	Essential hypertension
rs6981827	Efficacy	3	anastrozole	Breast Neoplasms
rs6990851	Efficacy	3	anastrozole	Breast Neoplasms
rs7387065	Efficacy	3	hydrochlorothiazide	Essential hypertension

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7387065	CSMD1	3	0.00	1	hydrochlorothiazide
rs11993031	CSMD1	3	0.00	1	hydrochlorothiazide
rs17070785	CSMD1		0.00	0
rs2617102	CSMD1		0.00	0
rs2954625	CSMD1		0.00	0
rs6981827	CSMD1	3	0.00	1	anastrozole
rs6990851	CSMD1	3	0.00	1	anastrozole

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases mutagenesis	3
Nickel	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	affects cotreatment, decreases methylation	1
mivebresib	decreases expression	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
testosterone undecanoate	affects cotreatment, increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Methamphetamine	affects response to substance	1
Methapyrilene	affects methylation	1
Tobacco Smoke Pollution	decreases expression	1
Levonorgestrel	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SJ79	HAP1 CSMD1 (-) 1	Cancer cell line	Male
CVCL_SJ80	HAP1 CSMD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder