WAPL

protein-coding

WAPL cohesin release factor, the group of Armadillo like helical domain containing

Gene summary

Enables ATP-dependent protein-DNA unloader activity. Involved in several processes, including mitotic sister chromatid segregation; negative regulation of DNA replication; and negative regulation of sister chromatid cohesion. Located in chromatin; cytoplasm; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

KIAA0261
WAPAL

MANE transcript

NM_015045.5

Inheritance

ClinVar variants

P:1U:129B:3

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr10:86,435,256-86,521,792

External References & Databases

Ensembl (ENSG00000062650)

Transcript & Mutation Effects

hg38 • Region Span ~86.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WAPL variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 13

Neurodevelopmental disorderTotal: 1

WAPL-related disorderTotal: 1

Ventricular septal defectTotal: 1

Macrocephaly at birthTotal: 1

PolyhydramniosTotal: 1

Large for gestational ageTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015045.5. 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
missense			116 clinvar	3 clinvar		119
nonsense			3 clinvar			3
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)	1 clinvar		3 clinvar			4
Total	1	0	129	3	0	133

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015045.5	RefSeq	NP_055860.1	18	MANE Select
ENST00000298767.10	Ensembl	ENSP00000298767.4	18	MANE Select
NM_001318328.2	RefSeq	NP_001305257.1	18	Standard
ENST00000372075.2	Ensembl	ENSP00000361145.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Establishment of Sister Chromatid Cohesion
S Phase
Mitotic Prometaphase
Separation of Sister Chromatids
Mitotic Anaphase

Biological Process

mitotic cell cycle
negative regulation of DNA replication
response to toxic substance
viral process
negative regulation of chromatin binding

Molecular Function

protein binding

Cellular Component

chromosome, centromeric region
chromatin
synaptonemal complex
nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298767
Coding exons: 18
Length: 86560
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125722
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.46	383	627	0.611	0.0000313	7915
Missense (PolyPhen)		80	260.94	0.30658		3276
Synonymous	1.04	199	218	0.911	0.0000108	2186
Loss of Function	6.72	2	56.5	0.0354	0.00000327	697

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)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin. Involved in both sister chromatid cohesion during interphase and sister- chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203}.;

Recessive Scores

pRec: 0.147

Intolerance Scores

RVIS EVS: -1.2
RVIS percentile EVS: 5.83

Essentials

Essential (gene trap): E