PGRMC2

Chr 4

progesterone receptor membrane component 2

Also known as: DG6, PMBP

The protein functions as an intracellular heme chaperone that delivers heme to the nucleus and regulates heme-responsive transcriptional repressors, while also playing roles in adipocyte function and glucose homeostasis. Mutations cause autosomal recessive primary ovarian insufficiency, affecting female reproductive development and function. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), suggesting intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
10
Pubs (1 yr)
27
P/LP submissions
0%
P/LP missense
0.59
LOEUF
Mechanism
Clinical SummaryPGRMC2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.68) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 40 VUS of 72 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.680
Z-score 2.30
OE 0.12 (0.040.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.84Z-score
OE missense 0.79 (0.680.93)
106 obs / 133.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.040.59)
00.351.4
Missense OE0.79 (0.680.93)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 1 / 8.0Missense obs/exp: 106 / 133.3Syn Z: -1.70

ClinVar Variant Classifications

72 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS40
Likely Benign1
26
Pathogenic
1
Likely Pathogenic
40
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
1
0
1
VUS
0
35
5
0
40
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total03533068

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

View in ClinVar →

Protein Context — Lollipop Plot

PGRMC2 · 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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