EPB41L4A

protein-coding

erythrocyte membrane protein band 4.1 like 4A, the group of FERM domain containing

Gene summary

The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

MANE transcript

NM_022140.5

Inheritance

—

ClinVar variants

P:2U:130B:17

Top phenotype

Primary ciliary dyskinesia

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr5:112,142,441-112,419,313

External References & Databases

Ensembl (ENSG00000129595)

Transcript & Mutation Effects

hg38 • Region Span ~276.9 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 EPB41L4A variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 116

not providedTotal: 19

Primary ciliary dyskinesiaTotal: 1

Spastic paraplegiaTotal: 1

Failure to thriveTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022140.5. 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			2 clinvar	4 clinvar	2 clinvar	8
missense		1 clinvar	119 clinvar	8 clinvar	3 clinvar	131
nonsense						0
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	2	130	12	5	149

Highest pathogenic variant AF is 0.000013014539

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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_022140.5	RefSeq	NP_071423.4	23	MANE Select
ENST00000261486.6	Ensembl	ENSP00000261486.5	23	MANE Select
NM_001347887.2	RefSeq	NP_001334816.1	24	Standard
NM_001347888.2	RefSeq	NP_001334817.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process
actomyosin structure organization

Molecular Function

molecular_function
cytoskeletal protein binding

Cellular Component

cellular_component
cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261486
Coding exons: 23
Length: 276876
Individuals with no LoFs: 124624
Homozygous LoFs: 0
Heterozygous LoFs: 175
Defined: 124799
p: 0.000701

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.26	451	382	1.18	0.0000219	4460
Missense (PolyPhen)		149	132.53	1.1242		1443
Synonymous	-1.54	158	135	1.17	0.00000773	1251
Loss of Function	1.46	38	49.1	0.774	0.00000277	567

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00057	0.00056	rare
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.00082	0.00082	rare
South Asian	0.00093	0.00092	rare
Other	0.00066	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.255
RVIS EVS: 1.61
RVIS percentile EVS: 95.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.128

Gene Damage Prediction

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