RAD54L

protein-coding

RAD54 like

Gene summary

The protein encoded by this gene belongs to the DEAD-like helicase superfamily, and shares similarity with Saccharomyces cerevisiae Rad54, a protein known to be involved in the homologous recombination and repair of DNA. This protein has been shown to play a role in homologous recombination related repair of DNA double-strand breaks. The binding of this protein to double-strand DNA induces a DNA topological change, which is thought to facilitate homologous DNA paring, and stimulate DNA recombination. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Dec 2008]

MANE transcript

NM_003579.4

Inheritance

—

ClinVar variants

P:10U:679B:392

Top phenotype

Hereditary breast ovarian cancer syndrome

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr1:46,246,461-46,278,480

External References & Databases

Ensembl (ENSG00000085999)

Transcript & Mutation Effects

hg38 • Region Span ~32.0 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 RAD54L variants in ClinVar

17 Conditions Cataloged

not specifiedTotal: 1045

Hereditary breast ovarian cancer syndromeTotal: 36

not providedTotal: 22

Familial cancer of breastTotal: 11

RAD54L-related disorderTotal: 9

Non-Hodgkin lymphomaTotal: 4

Premature ovarian failureTotal: 3

Germ cell tumorTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003579.4. 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	335 clinvar		336
missense	3 clinvar	5 clinvar	668 clinvar	55 clinvar		731
nonsense		1 clinvar	1 clinvar	1 clinvar		3
start loss						0
frameshift		1 clinvar	3 clinvar	1 clinvar		5
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	3	7	679	392	0	1081

Highest pathogenic variant AF is 0.000108423315

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003579.4	RefSeq	NP_003570.2	18	MANE Select
ENST00000371975.9	Ensembl	ENSP00000361043.4	18	MANE Select
NM_001142548.2	RefSeq	NP_001136020.1	18	Standard
NM_001370766.1	RefSeq	NP_001357695.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Homologous recombination - Homo sapiens (human)
Integrated Breast Cancer Pathway

Biological Process

double-strand break repair via homologous recombination
DNA strand renaturation
DNA repair
DNA recombination
determination of adult lifespan

Molecular Function

DNA binding
helicase activity
protein binding
ATP binding
annealing helicase activity

Cellular Component

nucleus
nucleoplasm
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371975
Coding exons: 18
Length: 30786
Individuals with no LoFs: 125448
Homozygous LoFs: 2
Heterozygous LoFs: 298
Defined: 125748
p: 0.00119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.252	424	410	1.04	0.0000267	4883
Missense (PolyPhen)		187	171.12	1.0928		2060
Synonymous	-0.268	158	154	1.03	0.00000846	1475
Loss of Function	1.71	29	40.8	0.711	0.00000257	456

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.00075	0.00072	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0044	0.0042	notable
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00067	0.00066	rare
South Asian	0.0035	0.0033	notable
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in DNA repair and mitotic recombination. Functions in the recombinational DNA repair (RAD52) pathway. Dissociates RAD51 from nucleoprotein filaments formed on dsDNA. Could be involved in the turnover of RAD51 protein-dsDNA filaments (By similarity). May play also an essential role in telomere length maintenance and telomere capping in mammalian cells. {ECO:0000250, ECO:0000269|PubMed:11459989, ECO:0000269|PubMed:12205100, ECO:0000269|PubMed:9774452}.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.160
RVIS EVS: -0.37
RVIS percentile EVS: 28.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.576

Gene Damage Prediction

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