HAGH

protein-coding

hydroxyacylglutathione hydrolase, the group of MBL domain containing glyoxalase 2 subfamily

Gene summary

The enzyme encoded by this gene is classified as a thiolesterase and is responsible for the hydrolysis of S-lactoyl-glutathione to reduced glutathione and D-lactate. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

MANE transcript

NM_005326.6

Inheritance

—

ClinVar variants

U:58B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr16:1,795,620-1,827,157

External References & Databases

Ensembl (ENSG00000063854)

Transcript & Mutation Effects

hg38 • Region Span ~31.5 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 HAGH variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 51

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005326.6. 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			1
missense			54 clinvar	2 clinvar		56
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	58	2	0	60

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005326.6	RefSeq	NP_005317.2	9	MANE Select
ENST00000397356.8	Ensembl	ENSP00000380514.3	9	MANE Select
NM_001040427.2	RefSeq	NP_001035517.1	8	Standard
NM_001286249.2	RefSeq	NP_001273178.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyruvate metabolism - Homo sapiens (human)
Pyruvate Dehydrogenase Complex Deficiency
Primary hyperoxaluria II, PH2
Pyruvate kinase deficiency
Leigh Syndrome

Biological Process

pyruvate metabolic process
glutathione biosynthetic process
methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione

Molecular Function

hydroxyacylglutathione hydrolase activity
protein binding
metal ion binding

Cellular Component

mitochondrial matrix
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397356
Coding exons: 9
Length: 31575
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.12	233	190	1.23	0.0000124	1973
Missense (PolyPhen)		88	72.046	1.2214		728
Synonymous	-1.92	107	84.5	1.27	0.00000628	638
Loss of Function	1.49	8	14.0	0.571	5.89e-7	185

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00080	0.00079	rare
East Asian	0	0.0	absent
Finnish	0.00021	0.00018	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Thiolesterase that catalyzes the hydrolysis of S-D- lactoyl-glutathione to form glutathione and D-lactic acid.;

Recessive Scores

pRec: 0.301

Intolerance Scores

LoFtool: 0.160
RVIS EVS: -0.11
RVIS percentile EVS: 45.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.956

Gene Damage Prediction

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