FCHSD2

protein-coding

FCH and double SH3 domains 2, the group of F-BAR domain containing

Gene summary

Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in clathrin-dependent endocytosis and positive regulation of Arp2/3 complex-mediated actin nucleation. Located in clathrin-coated pit and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

SH3MD3

MANE transcript

NM_014824.3

Inheritance

—

ClinVar variants

U:102B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr11:72,836,745-73,142,318

External References & Databases

Ensembl (ENSG00000137478)

Transcript & Mutation Effects

hg38 • Region Span ~305.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FCHSD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014824.3. 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			3 clinvar		2 clinvar	5
missense			99 clinvar		1 clinvar	100
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	102	0	3	105

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014824.3	RefSeq	NP_055639.2	20	MANE Select
ENST00000409418.9	Ensembl	ENSP00000386722.4	20	MANE Select
ENST00000311172.11	Ensembl	ENSP00000308978.7	17	Standard
ENST00000311172.12	Ensembl	ENSP00000308978.7	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

neuromuscular synaptic transmission
regulation of actin filament polymerization

Molecular Function

protein binding

Cellular Component

neuromuscular junction
recycling endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409418
Coding exons: 20
Length: 305517
Individuals with no LoFs: 125577
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125593
p: 0.0000637

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.84	289	392	0.738	0.0000212	4839
Missense (PolyPhen)		68	130.57	0.52079		1750
Synonymous	0.424	134	140	0.954	0.00000758	1341
Loss of Function	4.95	10	46.4	0.216	0.00000252	548

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.846
RVIS EVS: -0.89
RVIS percentile EVS: 10.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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