PGRMC1

protein-coding

progesterone receptor membrane component 1, the group of Membrane associated progesterone receptor family

Gene summary

This gene encodes a putative membrane-associated progesterone steroid receptor. The protein is expressed predominantly in the liver and kidney. [provided by RefSeq, Mar 2010]

MANE transcript

NM_006667.5

Inheritance

XL, AD

ClinVar variants

P:2U:45B:2

Top phenotype

Genetic non-acquired premature ovarian failure

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:119,236,245-119,244,466

External References & Databases

Ensembl (ENSG00000101856)

Transcript & Mutation Effects

hg38 • Region Span ~8.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataractMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0005129

Submitter: PanelApp Australia

primary ovarian failureLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005387

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PGRMC1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 27

Genetic non-acquired premature ovarian failureTotal: 3

not providedTotal: 2

PGRMC1-related disorderTotal: 2

Congenital portosystemic shuntTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006667.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar		1 clinvar	4
missense		2 clinvar	37 clinvar	1 clinvar		40
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	2	45	1	1	49

Highest pathogenic variant AF is 0.00007048981

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006667.5	RefSeq	NP_006658.1	3	MANE Select
ENST00000217971.8	Ensembl	ENSP00000217971.7	3	MANE Select
NM_001282621.2	RefSeq	NP_001269550.1	2	Standard
ENST00000535419.2	Ensembl	ENSP00000442821.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Neutrophil degranulation
Innate Immune System

Biological Process

neutrophil degranulation

Molecular Function

amyloid-beta binding
steroid binding
protein binding

Cellular Component

endoplasmic reticulum
plasma membrane
integral component of plasma membrane
membrane
smooth endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217971
Coding exons: 3
Length: 8214
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0800	78	80.0	0.975	0.00000553	1271
Missense (PolyPhen)		20	29.228	0.68427		473
Synonymous	1.15	28	36.8	0.760	0.00000268	402
Loss of Function	1.76	0	3.62	0.00	2.28e-7	68

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of a progesterone-binding protein complex (PubMed:28396637). Binds progesterone (PubMed:25675345). Has many reported cellular functions (heme homeostasis, interaction with CYPs). {ECO:0000269|PubMed:25675345, ECO:0000303|PubMed:28396637}.;

Recessive Scores

pRec: 0.229

Intolerance Scores

LoFtool: 0.204
RVIS EVS: 0.13
RVIS percentile EVS: 62.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.573

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium