AHNAK

protein-coding

AHNAK nucleoprotein, the group of PDZ domain containing

Gene summary

The protein encoded by this gene is a large (700 kDa) structural scaffold protein consisting of a central domain with 128 aa repeats. The encoded protein may play a role in such diverse processes as blood-brain barrier formation, cell structure and migration, cardiac calcium channel regulation, and tumor metastasis. A much shorter variant encoding a 17 kDa isoform exists for this gene, and the shorter isoform initiates a feedback loop that regulates alternative splicing of this gene. [provided by RefSeq, Oct 2016]

MANE transcript

NM_001620.3

Inheritance

—

ClinVar variants

U:932B:177

Top phenotype

AHNAK-related disorder

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr11:62,433,542-62,556,235

External References & Databases

Ensembl (ENSG00000124942)

Transcript & Mutation Effects

hg38 • Region Span ~122.7 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 AHNAK variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 978

not providedTotal: 141

AHNAK-related disorderTotal: 4

Hirschsprung disease, susceptibility to, 1Total: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001620.3. 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			2 clinvar	52 clinvar	19 clinvar	73
missense			925 clinvar	80 clinvar	26 clinvar	1031
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	932	132	45	1109

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001620.3	RefSeq	NP_001611.1	3	MANE Select
ENST00000378024.9	Ensembl	ENSP00000367263.4	3	MANE Select
NM_001346445.2	RefSeq	NP_001333374.1	3	Standard
NM_001346446.2	RefSeq	NP_001333375.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1

Biological Process

regulation of RNA splicing
protein complex oligomerization
regulation of voltage-gated calcium channel activity

Molecular Function

RNA binding
protein binding
S100 protein binding
cadherin binding
structural molecule activity conferring elasticity

Cellular Component

nucleus
cytoplasm
lysosomal membrane
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378024
Coding exons: 3
Length: 122692
Individuals with no LoFs: 125643
Homozygous LoFs: 0
Heterozygous LoFs: 105
Defined: 125748
p: 0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.97	3534	3.07e+3	1.15	0.000156	39206
Missense (PolyPhen)		1365	1274.6	1.0709		16927
Synonymous	-1.33	1201	1.14e+3	1.05	0.0000655	11579
Loss of Function	6.84	18	86.7	0.208	0.00000419	1788

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00093	0.00093	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00098	0.00098	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00039	0.00039	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be required for neuronal cell differentiation.;

Intolerance Scores

LoFtool: 0.303
RVIS EVS: -2.83
RVIS percentile EVS: 0.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

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