SLC44A4

Chr 6AD

solute carrier family 44 member 4

Also known as: C6orf29, CTL4, DFNA72, NG22, TPPT, hTPPT1

NCBI Gene: 80736ENSG00000204385UniProt: Q53GD3

The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 72MIM #617606
AD
321
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC44A4
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 166 VUS of 321 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.91LOEUF
pLI 0.000
Z-score 2.05
OE 0.67 (0.49–0.91)
Tolerant

Typical tolerance to LoF variation

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.
1.11Z-score
OE missense 0.84 (0.77–0.92)
344 obs / 407.2 exp
Tolerant

Mild missense constraint

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.0.67 (0.49–0.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.77–0.92)
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.0.85
0≤1.21.6
LoF obs/exp: 29 / 43.6Missense obs/exp: 344 / 407.2Syn Z: 1.57

ClinVar Variant Classifications

321 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS166
Likely Benign87
Benign56
Conflicting4
6
Pathogenic
2
Likely Pathogenic
166
VUS
87
Likely Benign
56
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
7
142
15
2
166
Likely Benign
1
5
47
34
87
Benign
0
12
34
10
56
Conflicting
—4
Total815910446321

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC44A4 · 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

?Deafness, autosomal dominant 72

MIM #617606

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer's disease: findings based on urine proteomics and machine learning.
Wang Y et al.·Alzheimers Res Ther
2023
[Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer].
Xu J et al.·Zhejiang Da Xue Xue Bao Yi Xue Ban
2025Review
Enterohemorrhagic Escherichia coli infection inhibits colonic thiamin pyrophosphate uptake via transcriptional mechanism.
Anandam KY et al.·PLoS One
2019Functional
SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss.
Ma Z et al.·Hum Mol Genet
2017
A phase 1 clinical trial of ASG-5ME, a novel drug-antibody conjugate targeting SLC44A4, in patients with advanced pancreatic and gastric cancers.
Coveler AL et al.·Invest New Drugs
2016Clinical trial
The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma.
Kang W et al.·Biomed Res Int
2020
Treatment of genetic defects of thiamine transport and metabolism.
Ortigoza-Escobar JD et al.·Expert Rev Neurother
2016Review
Novel agents in the treatment of pancreatic adenocarcinoma.
Dimou A et al.·JOP
2013Review
A Circadian Rhythm-related Signature to Predict Prognosis, Immune Infiltration, and Drug Response in Breast Cancer.
Chu M et al.·Curr Med Chem
2025
A promising natural killer cell-based model and a nomogram for the prognostic prediction of clear-cell renal cell carcinoma.
Yao Q et al.·Eur J Med Res
2024Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SLC44A4 modulates the extracellular matrix through the PI3K/AKT signaling pathway, thereby affecting the proliferation, migration, and invasion of ovarian clear cell carcinoma (OCCC).
Li T et al.·Cytotechnology
2026
A new combined prognostic model involving SLC44A4 improves the predictive ability for colorectal cancer patients.
Li P et al.·Transl Cancer Res
2025🔓 Open AccessCohort
Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology.
Sabui S et al.·Am J Physiol Gastrointest Liver Physiol
2024Functional
Association between SLC44A4-NOTCH4 SNPs and serum lipid levels in the Chinese Han and Maonan ethnic groups.
Zheng PF et al.·Nutr Metab (Lond)
2020🔓 Open Access
A phase I study of the antibody drug conjugate ASG-5ME, an SLC44A4-targeting antibody carrying auristatin E, in metastatic castration-resistant prostate cancer.
McHugh D et al.·Invest New Drugs
2019
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