FRMPD2

protein-coding

FERM and PDZ domain containing 2, the group of FERM domain containing|PDZ domain containing

Gene summary

This gene encodes a peripheral membrane protein and is located in a region of chromosome 10q that contains a segmental duplication. This copy of the gene is full-length and is in the telomeric duplicated region. Two other more centromerically proximal copies of the gene are partial and may represent pseudogenes. This full-length gene appears to function in the establishment and maintenance of cell polarization. The protein is recruited to cell-cell junctions in an E-cadherin-dependent manner, and is selectively localized at the basolateral membrane in polarized epithelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2009]

Previous symbols:

PDZD5C
PDZK5C

MANE transcript

NM_001018071.4

Inheritance

—

ClinVar variants

U:174B:27

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr10:48,153,088-48,274,696

External References & Databases

Ensembl (ENSG00000170324)

Transcript & Mutation Effects

hg38 • Region Span ~121.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FRMPD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 183

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001018071.4. 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			1 clinvar	9 clinvar		10
missense			172 clinvar	16 clinvar	2 clinvar	190
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	174	25	2	201

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001018071.4	RefSeq	NP_001018081.4	29	MANE Select
ENST00000374201.8	Ensembl	ENSP00000363317.3	29	MANE Select
NM_001042512.3	RefSeq	NP_001035977.3	6	Standard
NM_001318191.1	RefSeq	NP_001305120.1	27	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

bicellular tight junction assembly

Molecular Function

protein binding
1-phosphatidylinositol binding

Cellular Component

cytoplasm
cytoskeleton
bicellular tight junction
basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374201
Coding exons: 29
Length: 118341
Individuals with no LoFs: 125414
Homozygous LoFs: 15
Heterozygous LoFs: 319
Defined: 125748
p: 0.00133

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.750	625	574	1.09	0.0000307	8465
Missense (PolyPhen)		176	167.77	1.0491		2659
Synonymous	-1.26	245	221	1.11	0.0000121	2587
Loss of Function	0.468	51	54.7	0.932	0.00000250	789

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0030	0.0030	notable
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.00014	0.000099	rare
East Asian	0.00092	0.00092	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0016	0.0014	notable
South Asian	0.0022	0.0021	notable
Other	0.0017	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the regulation of tight junction formation. Binds phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). {ECO:0000269|PubMed:19706687}.;

Recessive Scores

pRec: 0.0910

Intolerance Scores

LoFtool: 0.895
RVIS EVS: -0.65
RVIS percentile EVS: 16.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.218

Gene Damage Prediction

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