AHNAK2

protein-coding

AHNAK nucleoprotein 2, the group of PDZ domain containing

Gene summary

This gene encodes a large nucleoprotein. The encoded protein has a tripartite domain structure with a relatively short N-terminus and a long C-terminus, separated by a large body of repeats. The N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain is thought to function in the formation of stable homodimers. The encoded protein may play a role in calcium signaling by associating with calcium channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

Previous symbols:

C14orf78

MANE transcript

NM_138420.4

Inheritance

ClinVar variants

U:1538B:678

Top phenotype

AHNAK2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr14:104,937,244-104,978,374

External References & Databases

Ensembl (ENSG00000185567)

Transcript & Mutation Effects

hg38 • Region Span ~41.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Charcot-Marie-Tooth diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015626

Submitter: Illumina

Charcot-Marie-Tooth diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015626

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AHNAK2 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 1800

not providedTotal: 484

AHNAK2-related disorderTotal: 5

Abnormality of neuronal migrationTotal: 2

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

DysmetriaTotal: 1

MigraineTotal: 1

Enhancement of the C-reflexTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138420.4. 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			9 clinvar	229 clinvar	29 clinvar	267
missense			1523 clinvar	372 clinvar	44 clinvar	1939
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar	3 clinvar	1 clinvar	7
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	1538	604	74	2216

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138420.4	RefSeq	NP_612429.2	7	MANE Select
ENST00000333244.6	Ensembl	ENSP00000353114.4	7	MANE Select
NM_001350929.2	RefSeq	NP_001337858.1	4	Standard
ENST00000557457.1	Ensembl	ENSP00000450998.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

plasma membrane repair
regulation of RNA splicing

Molecular Function

protein binding

Cellular Component

nucleus
cytoplasm
cytosol
plasma membrane
Z disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333244
Coding exons: 7
Length: 41114
Individuals with no LoFs: 124612
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 124632
p: 0.0000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-12.2	5006	3.09e+3	1.62	0.000185	37051
Missense (PolyPhen)		1197	758.67	1.5778		9817
Synonymous	-22.2	2382	1.35e+3	1.77	0.0000985	11684
Loss of Function	1.54	7	13.0	0.538	7.01e-7	152

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000056	0.000056	rare
Finnish	0.000050	0.000046	rare
European (Non-Finnish)	0.000082	0.000080	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.908
RVIS EVS: 27.6
RVIS percentile EVS: 99.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0502

Gene Damage Prediction

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