CSMD3

protein-coding

CUB and Sushi multiple domains 3, the group of Sushi domain containing|Complement system regulators and receptors

Gene summary

Predicted to be involved in regulation of dendrite development. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_198123.2

Inheritance

ClinVar variants

U:454B:64

Top phenotype

CSMD3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr8:112,222,928-113,436,939

External References & Databases

Ensembl (ENSG00000164796)

Transcript & Mutation Effects

hg38 • Region Span ~1,214.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSMD3 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 417

CSMD3-related disorderTotal: 76

not providedTotal: 48

Familial meningiomaTotal: 4

Pachygyria-intellectual disability-epilepsy syndromeTotal: 2

CSMD3-associated Hirschsprung diseaseTotal: 1

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198123.2. 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	27 clinvar	15 clinvar	47
missense			443 clinvar	12 clinvar	10 clinvar	465
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	454	39	25	518

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198123.2	RefSeq	NP_937756.1	71	MANE Select
ENST00000297405.10	Ensembl	ENSP00000297405.5	71	MANE Select
NM_001363185.1	RefSeq	NP_001350114.1	67	Standard
NM_052900.3	RefSeq	NP_443132.3	69	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of dendrite development

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000297405
Coding exons: 71
Length: 1214172
Individuals with no LoFs: 125672
Homozygous LoFs: 0
Heterozygous LoFs: 76
Defined: 125748
p: 0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.14	1813	1.95e+3	0.927	0.000101	24216
Missense (PolyPhen)		710	868.58	0.81743		10769
Synonymous	-2.61	760	674	1.13	0.0000349	7132
Loss of Function	9.96	46	197	0.234	0.0000106	2374

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00079	0.00079	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00030	0.00030	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in dendrite development. {ECO:0000250|UniProtKB:Q80T79}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.585
RVIS EVS: -3.49
RVIS percentile EVS: 0.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.758

Gene Damage Prediction

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