ANKHD1

protein-coding

ankyrin repeat and KH domain containing 1, the group of Ankyrin repeat domain containing

Gene summary

This gene encodes a protein with multiple ankyrin repeat domains and a single KH-domain. The protein is thought to function as a scaffolding protein, and it may be involved in the regulation of caspases and thereby play an antiapoptotic role in cell survival. Alternative splicing results in multiple transcript variants, one of which generates a fusion transcript (MASK-BP3) with the downstream eIF4E-binding protein 3 (EIF4EBP3) gene, resulting in a protein comprised of the ANKHD1 sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Sep 2010]

MANE transcript

NM_017747.3

Inheritance

—

ClinVar variants

U:28B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr5:140,401,814-140,539,856

External References & Databases

Ensembl (ENSG00000131503)

Transcript & Mutation Effects

hg38 • Region Span ~138.0 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 ANKHD1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 17

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017747.3. 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			4 clinvar	1 clinvar		5
missense			19 clinvar		1 clinvar	20
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	28	1	1	30

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017747.3	RefSeq	NP_060217.1	34	MANE Select
ENST00000360839.7	Ensembl	ENSP00000354085.2	34	MANE Select
NM_001197030.2	RefSeq	NP_001183959.1	10	Standard
NM_017978.3	RefSeq	NP_060448.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ankhd1	Danio rerio	Structure: atrium Quality: dilated abnormal

Gene / Model

Organism

Observed Phenotype

ankhd1

Danio rerio

Structure: atrium

Quality: dilated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

innate immune response

Molecular Function

RNA binding
protein binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000297183
Coding exons: 36
Length: 147765
Individuals with no LoFs: 124478
Homozygous LoFs: 1
Heterozygous LoFs: 48
Defined: 124527
p: 0.000197

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.47	886	1.35e+3	0.657	0.0000681	16924
Missense (PolyPhen)		135	253.3	0.53297		3146
Synonymous	0.941	468	495	0.946	0.0000253	5461
Loss of Function	9.00	6	106	0.0566	0.00000597	1311

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.0012	0.0011	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0.00016	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases. {ECO:0000269|PubMed:16098192}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.407
RVIS EVS: -2.36
RVIS percentile EVS: 1.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.991

Gene Damage Prediction

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