SIT1

Chr 9

solute carrier family 6 member 20

Also known as: IMINO, SIT1, XT3, Xtrp3

NCBI Gene: 54716ENSG00000137078UniProt: Q9NP91

Transport of small hydrophilic substances across cell membranes is mediated by substrate-specific transporter proteins which have been classified into several families of related genes. The protein encoded by this gene belongs to the sodium:neurotransmitter symporter (SNF) family and functions as a proline transporter expressed in kidney and small intestine. Mutations in this gene are associated with Hyperglycinuria and Iminoglycinuria. [provided by RefSeq, Jul 2020]

Primary Disease Associations & Inheritance

UniProtHyperglycinuria
UniProtIminoglycinuria
109
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SIT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 29 VUS of 109 total submissions

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.
1.19LOEUF
pLI 0.001
Z-score 1.16
OE 0.60 (0.33–1.19)
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.
1.17Z-score
OE missense 0.69 (0.58–0.83)
79 obs / 114.1 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.0.60 (0.33–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.58–0.83)
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.0.97
0≤1.21.6
LoF obs/exp: 6 / 10.0Missense obs/exp: 79 / 114.1Syn Z: 0.15

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic9
VUS29
Likely Benign3
64
Pathogenic
9
Likely Pathogenic
29
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
64
0
64
Likely Pathogenic
0
0
9
0
9
VUS
0
22
7
0
29
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total024801105

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

View in ClinVar →

Protein Context — Lollipop Plot

SIT1 · 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
SIT1 identifies circulating hypoactive T cells with elevated cytotoxic molecule secretion in systemic lupus erythematosus patients.
Hasimu A et al.·Immunol Res
2024Cohort
SIT1 transporter as a potential novel target in treatment of COVID-19.
Semiz S·Biomol Concepts
2021
Identifying Immune Response Protein Biomarkers in Parkinson's-Related Cognitive Impairment and Depression.
Su Q et al.·Mol Neurobiol
2025
Applications of the Microscale Thermophoresis Binding Assay in COVID-19 Research.
Nydegger DT et al.·Viruses
2023
Genotypic diversity of multidrug-, quinolone- and extensively drug-resistant Mycobacterium tuberculosis isolates in Thailand.
Disratthakit A et al.·Infect Genet Evol
2015
Bioinformatics analysis to screen key prognostic genes in the breast cancer tumor microenvironment.
Ye Q et al.·Bioengineered
2020
Tendon Yaw (TY) Angle: Direct Measurement of the Quadriceps Vector Resolves the Rotational Enigma of Recurrent Patellar Instability.
Nizić D et al.·Medicina (Kaunas)
2025
Genetic profiling of Mycobacterium tuberculosis revealed "modern" Beijing strains linked to MDR-TB from Southwestern Colombia.
Nieto Ramirez LM et al.·PLoS One
2020
The Energetic Saver Profile From Sit-to-Stand Does Not Persist During Very Low-Intensity Physical Activity in Healthy Men and Women.
Isacco L et al.·J Phys Act Health
2024
Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients.
Forrest A et al.·Antimicrob Agents Chemother
1993Clinical trial
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