ANKLE1

protein-coding

ankyrin repeat and LEM domain containing 1, the group of Ankyrin repeat domain containing|LEM domain containing|GIY-YIG endonuclease domain containing

Gene summary

Enables DNA endonuclease activity and metal ion binding activity. Involved in DNA damage response and protein export from nucleus. Located in cytosol; midbody; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

ANKRD41

MANE transcript

NM_152363.6

Inheritance

—

ClinVar variants

U:113B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.04

Max pathogenic AF

—

Genomic locus

chr19:17,281,645-17,287,646

External References & Databases

Ensembl (ENSG00000160117)

Transcript & Mutation Effects

hg38 • Region Span ~6.0 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 ANKLE1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 115

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152363.6. 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	1 clinvar		3
missense			108 clinvar	7 clinvar	3 clinvar	118
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	113	8	3	124

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152363.6	RefSeq	NP_689576.6	9	MANE Select
ENST00000404085.7	Ensembl	ENSP00000384008.3	9	MANE Select
NM_001278443.2	RefSeq	NP_001265372.2	9	Standard
NM_001278444.2	RefSeq	NP_001265373.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA repair
protein export from nucleus
nucleic acid phosphodiester bond hydrolysis
positive regulation of response to DNA damage stimulus

Molecular Function

endonuclease activity
protein binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394458
Coding exons: 9
Length: 6002
Individuals with no LoFs: 125543
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125592
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.855	324	370	0.875	0.0000213	3837
Missense (PolyPhen)		88	110.64	0.79535		1151
Synonymous	0.880	148	162	0.912	0.00000936	1364
Loss of Function	-0.168	26	25.1	1.04	0.00000125	257

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.00018	0.00014	rare
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.000069	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Endonuclease that probably plays a role in the DNA damage response and DNA repair. {ECO:0000269|PubMed:22399800, ECO:0000269|PubMed:27245214}.;

Recessive Scores

pRec: 0.0944

Intolerance Scores

LoFtool: 0.897
RVIS EVS: 2.8
RVIS percentile EVS: 99.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.154

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High