BPHL

protein-coding

biphenyl hydrolase like

Gene summary

This gene encodes a member of the serine protease family of hydrolytic enzymes which contain a serine in their active site. The encoded protein may play a role in activation of the antiviral prodrug valacyclovir. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jan 2009]

Previous symbols:

MCNAA

MANE transcript

NM_004332.4

Inheritance

—

ClinVar variants

U:53B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr6:3,118,374-3,153,599

External References & Databases

Ensembl (ENSG00000137274)

Transcript & Mutation Effects

hg38 • Region Span ~35.2 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 BPHL variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004332.4. 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			3 clinvar	1 clinvar		4
missense			46 clinvar	1 clinvar	1 clinvar	48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	53	2	1	56

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004332.4	RefSeq	NP_004323.2	7	MANE Select
ENST00000380379.10	Ensembl	ENSP00000369739.5	7	MANE Select
NM_001302777.1	RefSeq	NP_001289706.1	7	Standard
ENST00000380368.6	Ensembl	ENSP00000369726.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phase I - Functionalization of compounds
Biological oxidations
Metabolism

Biological Process

cellular amino acid metabolic process
xenobiotic metabolic process
response to toxic substance

Molecular Function

alpha-amino-acid esterase activity

Cellular Component

mitochondrion
mitochondrial outer membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380379
Coding exons: 7
Length: 35205
Individuals with no LoFs: 123246
Homozygous LoFs: 157
Heterozygous LoFs: 2345
Defined: 125748
p: 0.0100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.421	140	155	0.905	0.00000885	1879
Missense (PolyPhen)		49	46.3	1.0583		523
Synonymous	0.776	54	61.8	0.874	0.00000401	582
Loss of Function	0.626	11	13.5	0.816	7.21e-7	161

Population LoF Frequency

Population	CAF	p-value	Status
African	0.14	0.14	notable
Latino/Admixed American	0.0068	0.0064	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0016	0.0016	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00046	0.00046	rare
South Asian	0.0030	0.0029	notable
Other	0.0052	0.0049	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine hydrolase that catalyzes the hydrolytic activation of amino acid ester prodrugs of nucleoside analogs such as valacyclovir and valganciclovir. Activates valacyclovir to acyclovir. May play a role in detoxification processes. It is a specific alpha-amino acid ester hydrolase that prefers small, hydrophobic, and aromatic side chains and does not have a stringent requirement for the leaving group other than preferring a primary alcohol. {ECO:0000269|PubMed:18256025}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.719
RVIS EVS: 0.73
RVIS percentile EVS: 86.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.278

Gene Damage Prediction

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