SLC29A3

Chr 10

solute carrier family 29 member 3

Also known as: ENT3, HCLAP, HJCD, PHID

NCBI Gene: 55315ENSG00000198246UniProt: Q9BZD2

This gene encodes a nucleoside transporter. The encoded protein plays a role in cellular uptake of nucleosides, nucleobases, and their related analogs. Mutations in this gene have been associated with H syndrome, which is characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism. A related disorder, PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus), has also been associated with mutations at this locus. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

UniProtHistiocytosis-lymphadenopathy plus syndrome
586
ClinVar variants
64
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— SLC29A3
🧬
Gene-Disease Validity (ClinGen)
H syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
64 Pathogenic / Likely Pathogenic· 256 VUS of 586 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
1.32LOEUF
pLI 0.000
Z-score 0.65
OE 0.82 (0.52–1.32)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.48Z-score
OE missense 1.08 (0.98–1.19)
292 obs / 270.0 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.0.82 (0.52–1.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.98–1.19)
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.1.17
0≤1.21.6
LoF obs/exp: 12 / 14.7Missense obs/exp: 292 / 270.0Syn Z: -1.49

ClinVar Variant Classifications

586 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic17
VUS256
Likely Benign208
Benign36
Conflicting22
47
Pathogenic
17
Likely Pathogenic
256
VUS
208
Likely Benign
36
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
4
21
0
47
Likely Pathogenic
8
5
4
0
17
VUS
1
217
36
2
256
Likely Benign
0
10
48
150
208
Benign
0
5
23
8
36
Conflicting
—22
Total31241132160586

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC29A3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Compound heterozygous SLC29A3 mutation causes H syndrome in a Moroccan patient: A case report.
Bakhchane A et al.·Curr Res Transl Med
2016Review
A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review.
Rezaie N et al.·BMC Med Genomics
2024Review
Osteopetrosis: Gene-based nosology and significance Dysosteosclerosis.
Turan S·Bone
2023
Clinicogenetic characterisation of SLC29A3-related syndromes: a case series, tracing ancestral variants and molecular dynamics simulation.
Biglari S et al.·J Med Genet
2025Cohort
H syndrome: A histiocytosis-lymphadenopathy plus syndrome. A comprehensive review of the literature.
Hamad A et al.·Hematol Oncol Stem Cell Ther
2024Review
Atypical comorbidities in a child considered to have type 1 diabetes led to the diagnosis of SLC29A3 spectrum disorder.
Besci Ö et al.·Hormones (Athens)
2022Review
Genetics of the congenital absence of the vas deferens.
Bieth E et al.·Hum Genet
2021Review
Generalized pure cutaneous Rosai-Dorfman disease: a link between inflammation and cancer not associated with mitochondrial DNA and SLC29A3 gene mutation?
Zheng M et al.·Discov Med
2013Review
Whole exome sequencing for identifying rare genetic variants related to idiopathic granulomatous mastitis.
Ozer L et al.·Clin Rheumatol
2025
A novel homozygous frame-shift mutation in the SLC29A3 gene: a new case report and review of literature.
Noavar S et al.·BMC Med Genet
2019Review
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
H Syndrome

Histiocytosis and Inflammatory Manifestations in Patients with H Syndrome

RECRUITING
NCT06742073Rabin Medical CenterStarted 2024-11-01

External Resources

Links to major genomics databases and tools