PARM1

Chr 4

prostate androgen-regulated mucin-like protein 1

PARM1 encodes a protein that may regulate telomerase activity and cellular resistance to apoptosis, with localization to the Golgi apparatus, endosomes, and nucleoplasm. Loss-of-function variants in PARM1 are associated with autosomal recessive intellectual disability and developmental delay. The gene shows low constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.22
Clinical SummaryPARM1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.22LOEUF
pLI 0.001
Z-score 1.11
OE 0.62 (0.341.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.07Z-score
OE missense 0.98 (0.861.12)
162 obs / 164.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.341.22)
00.351.4
Missense OE0.98 (0.861.12)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 6 / 9.7Missense obs/exp: 162 / 164.7Syn Z: -1.40
DN
0.6161th %ile
GOF
0.6542th %ile
LOF
0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

PARM1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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