AHNAK

Chr 11

AHNAK nucleoprotein

Also known as: AHNAK1, AHNAKRS, PM227

NCBI Gene: 79026ENSG00000124942UniProt: Q09666

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]

492
ClinVar variants
0
Pathogenic / LP
0.90
pLI score
0
Active trials
Clinical Summary— AHNAK
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.90) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
434 VUS of 492 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.31LOEUF
pLI 0.898
Z-score 6.84
OE 0.21 (0.14–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-2.97Z-score
OE missense 1.15 (1.12–1.18)
3534 obs / 3071.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.14–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (1.12–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 18 / 86.7Missense obs/exp: 3534 / 3071.2Syn Z: -1.33

ClinVar Variant Classifications

492 submitted variants in ClinVar

ClinVar

Classification Summary

VUS434
Likely Benign53
Benign2
Conflicting3
434
VUS
53
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
433
1
0
434
Likely Benign
0
30
0
23
53
Benign
0
2
0
0
2
Conflicting
—3
Total0465123492

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AHNAK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer.
Xie R et al.·Cancer Res
2023
Comparative Analysis of Primary Sarcopenia and End-Stage Renal Disease-Related Muscle Wasting Using Multi-Omics Approaches.
Setoyama D et al.·J Cachexia Sarcopenia Muscle
2025
Neuropeptide Y regulates osteocyte phenotype and function through AHNAK-Smad signalling.
Wu X et al.·J Mol Endocrinol
2023
Advancing personalized, predictive, and preventive medicine in bladder cancer: a multi-omics and machine learning approach for novel prognostic modeling, immune profiling, and therapeutic target discovery.
Yan H et al.·Front Immunol
2025Functional
Interaction between TMEFF1 and AHNAK proteins in ovarian cancer cells: Implications for clinical prognosis.
Nie X et al.·Int Immunopharmacol
2022
Identification of distinct genomic features reveals frequent somatic AHNAK and PTEN mutations predominantly in primary malignant melanoma presenting in the ureter.
Huang Y et al.·Jpn J Clin Oncol
2022Review
Integrative analysis reveals different feature of intrahepatic cholangiocarcinoma subtypes.
Chen Z et al.·Liver Int
2024
Diagnostic and prognostic value of STAP1 and AHNAK methylation in peripheral blood immune cells for HBV-related hepatopathy.
Sun L et al.·Front Immunol
2023
Single-cell transcriptomic analysis reveals distinct plasma cell populations in chronic thromboembolic pulmonary hypertension.
Zhang R et al.·J Thromb Haemost
2025
Silencing AHNAK promotes nasopharyngeal carcinoma progression by upregulating the ANXA2 protein.
Lu X et al.·Cell Oncol (Dordr)
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools