CSMD1

protein-coding

CUB and Sushi multiple domains 1, the group of Protein phosphatase 1 regulatory subunits|Complement system regulators and receptors|Sushi domain containing

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_033225.6

Inheritance

AR, AD

ClinVar variants

P:2U:843B:164

Top phenotype

CSMD1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr8:2,935,353-4,994,972

External References & Databases

Ensembl (ENSG00000183117)

Transcript & Mutation Effects

hg38 • Region Span ~2,059.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSMD1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 769

not providedTotal: 189

CSMD1-related disorderTotal: 121

CSMD1-associated neurodevelopmental disorderTotal: 2

Cerebellar ataxiaTotal: 1

Autism spectrum disorderTotal: 1

Large for gestational ageTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033225.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	85 clinvar	40 clinvar	130
missense		1 clinvar	818 clinvar	28 clinvar	11 clinvar	858
nonsense	1 clinvar		7 clinvar			8
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	1	1	843	113	51	1009

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033225.6	RefSeq	NP_150094.5	70	MANE Select
ENST00000635120.2	Ensembl	ENSP00000489225.1	70	MANE Select
ENST00000335551.11	Ensembl	ENSP00000334828.6	56	Standard
ENST00000400186.7	Ensembl	ENSP00000383047.3	68	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

startle response
glucose homeostasis

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000537824
Coding exons: 70
Length: 2059620
Individuals with no LoFs: 125645
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125696
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-6.87	2787	1.94e+3	1.44	0.000112	23041
Missense (PolyPhen)		1120	959.08	1.1678		11311
Synonymous	-16.5	1395	801	1.74	0.0000557	6770
Loss of Function	10.4	27	177	0.153	0.00000922	2109

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00049	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000049	0.000046	rare
European (Non-Finnish)	0.00020	0.00018	rare
South Asian	0.00030	0.00026	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potential suppressor of squamous cell carcinomas.;

Recessive Scores

pRec: 0.124

Intolerance Scores

RVIS EVS: -7.11
RVIS percentile EVS: 0.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.746

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium