FEM1A

protein-coding

fem-1 homolog A, the group of Ankyrin repeat domain containing

Gene summary

Enables EP4 subtype prostaglandin E2 receptor binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in negative regulation of inflammatory response and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in Golgi apparatus and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. Is active in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_018708.3

Inheritance

—

ClinVar variants

U:79B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr19:4,791,734-4,801,273

External References & Databases

Ensembl (ENSG00000141965)

Transcript & Mutation Effects

hg38 • Region Span ~9.5 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 FEM1A variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 80

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018708.3. 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						0
missense			79 clinvar	1 clinvar		80
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	79	1	0	80

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018708.3	RefSeq	NP_061178.1	1	MANE Select
ENST00000269856.5	Ensembl	ENSP00000269856.3	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Neddylation

Biological Process

protein ubiquitination
post-translational protein modification
negative regulation of inflammatory response
regulation of ubiquitin-protein transferase activity

Molecular Function

ubiquitin-protein transferase activity
EP4 subtype prostaglandin E2 receptor binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269856
Coding exons: 1
Length: 3844
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.42	311	390	0.797	0.0000248	4267
Missense (PolyPhen)		93	163.77	0.56786		1837
Synonymous	0.0475	184	185	0.996	0.0000131	1441
Loss of Function	0.407	15	16.8	0.893	8.08e-7	188

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit (By similarity). May participate in antiinflammatory signaling via its interaction with PTGER4. {ECO:0000250}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.590
RVIS EVS: 0
RVIS percentile EVS: 53.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.924

Gene Damage Prediction

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