FEM1B

protein-coding

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

Gene summary

This gene encodes an ankyrin repeat protein that belongs to the death receptor-associated family of proteins and plays a role in mediating apoptosis. The encoded protein is also thought to function in the replication stress-induced checkpoint signaling pathway via interaction with checkpoint kinase 1. [provided by RefSeq, Aug 2013]

MANE transcript

NM_015322.5

Inheritance

ClinVar variants

P:1U:51B:2

Top phenotype

syndromic disease

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr15:68,277,745-68,295,862

External References & Databases

Ensembl (ENSG00000169018)

Transcript & Mutation Effects

hg38 • Region Span ~18.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic diseaseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0002254

Submitter: PanelApp Australia

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FEM1B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 38

not providedTotal: 13

Neurodevelopmental disorder with behavioral, ear, and skeletal abnormalitiesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015322.5. 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			1 clinvar		1 clinvar	2
missense	1 clinvar		49 clinvar	1 clinvar		51
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	51	1	1	54

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015322.5	RefSeq	NP_056137.1	2	MANE Select
ENST00000306917.5	Ensembl	ENSP00000307298.4	2	MANE Select
ENST00000566008.1	Ensembl	ENSP00000456968.1	2	Standard
ENST00000566739.1	Ensembl	ENSP00000457342.1	1	Standard

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

apoptotic process
protein ubiquitination
post-translational protein modification
regulation of ubiquitin-protein transferase activity
branching involved in prostate gland morphogenesis

Molecular Function

ubiquitin-protein transferase activity
death receptor binding
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306917
Coding exons: 2
Length: 18063
Individuals with no LoFs: 125744
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125748
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.62	160	351	0.456	0.0000184	4145
Missense (PolyPhen)		32	130.2	0.24578		1512
Synonymous	-0.409	139	133	1.05	0.00000694	1244
Loss of Function	2.99	4	17.5	0.228	9.81e-7	226

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	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit. Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis. Also involved in glucose homeostasis in pancreatic islet. Functions as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1. {ECO:0000269|PubMed:10542291, ECO:0000269|PubMed:19330022}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.948

Gene Damage Prediction

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