PMS1

Chr 2

PMS1 homolog 1, mismatch repair system component

Also known as: HNPCC3, MLH2, PMSL1, hPMS1

This protein is involved in DNA mismatch repair and can form heterodimers with MLH1. Mutations cause hereditary nonpolyposis colorectal cancer type 3 (Lynch syndrome), which follows autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.01
Clinical SummaryPMS1
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Gene-Disease Validity (ClinGen)
Lynch syndrome · ADRefuted

Refuted — evidence has disproved this relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.48
OE 0.76 (0.571.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.62Z-score
OE missense 0.92 (0.850.99)
441 obs / 479.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.571.01)
00.351.4
Missense OE0.92 (0.850.99)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 32 / 42.4Missense obs/exp: 441 / 479.5Syn Z: 1.61
DN
0.6843th %ile
GOF
0.3094th %ile
LOF
0.4234th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PMS1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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