HAGHL

Summary

HAGHL (hydroxyacylglutathione hydrolase like, HGNC:14177) is a protein-coding gene on chromosome 16p13.3, encoding Hydroxyacylglutathione hydrolase-like protein (Q6PII5). Hydrolase acting on ester bonds.

Predicted to enable hydroxyacylglutathione hydrolase activity. Predicted to be involved in methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione.

Source: NCBI Gene 84264 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_032304

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14177
Approved symbol	HAGHL
Name	hydroxyacylglutathione hydrolase like
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC2605
Ensembl gene	ENSG00000103253
Ensembl biotype	protein_coding
Entrez	84264

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 27 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000341413, ENST00000389701, ENST00000389703, ENST00000549114, ENST00000561546, ENST00000561561, ENST00000561750, ENST00000562141, ENST00000562187, ENST00000563156, ENST00000563792, ENST00000564537, ENST00000564545, ENST00000567414, ENST00000567696, ENST00000568141, ENST00000569143, ENST00000569385, ENST00000569604, ENST00000647875, ENST00000905744, ENST00000905745, ENST00000905746, ENST00000905747, ENST00000905748, ENST00000905749, ENST00000905750, ENST00000917737, ENST00000917738, ENST00000917739, ENST00000917740, ENST00000917741, ENST00000917742, ENST00000917743, ENST00000917744, ENST00000971660

RefSeq mRNA: 7 — MANE Select: NM_032304 NM_001290137, NM_001290139, NM_001323635, NM_001323636, NM_001365282, NM_032304, NM_207112

CCDS: CCDS32354, CCDS32355, CCDS92077

Canonical transcript exons

ENST00000389703 — 8 exons

Exon	Start	End
ENSE00000664192	728316	728424
ENSE00002395574	727106	727614
ENSE00003470347	727965	728029
ENSE00003509353	729009	729088
ENSE00003530061	728116	728233
ENSE00003582146	728504	728604
ENSE00003678116	729288	729715
ENSE00003789541	728794	728895

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8327 / max 108.5483, expressed in 1603 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151989	1.9017	996
151993	1.8400	749
151991	1.7219	816
151990	0.8879	561
151992	0.3085	151
207697	0.1726	104

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	97.70	gold quality
right uterine tube	UBERON:0001302	96.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.79	gold quality
caudate nucleus	UBERON:0001873	93.22	gold quality
putamen	UBERON:0001874	93.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.93	gold quality
right frontal lobe	UBERON:0002810	92.52	gold quality
apex of heart	UBERON:0002098	92.33	gold quality
cerebellar hemisphere	UBERON:0002245	91.90	gold quality
cerebellar cortex	UBERON:0002129	91.69	gold quality
spinal cord	UBERON:0002240	91.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.39	gold quality
nucleus accumbens	UBERON:0001882	90.98	gold quality
anterior cingulate cortex	UBERON:0009835	90.95	gold quality
cerebellum	UBERON:0002037	90.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.14	gold quality
hypothalamus	UBERON:0001898	89.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.95	gold quality
substantia nigra	UBERON:0002038	88.81	gold quality
prefrontal cortex	UBERON:0000451	88.62	gold quality
amygdala	UBERON:0001876	88.32	gold quality
adenohypophysis	UBERON:0002196	88.29	gold quality
neocortex	UBERON:0001950	87.86	gold quality
frontal cortex	UBERON:0001870	87.78	gold quality
pituitary gland	UBERON:0000007	87.75	gold quality
brain	UBERON:0000955	87.26	gold quality
forebrain	UBERON:0001890	87.26	gold quality
midbrain	UBERON:0001891	86.54	gold quality
cerebral cortex	UBERON:0000956	86.29	gold quality
spleen	UBERON:0002106	84.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

3 targeting HAGHL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-874-5P	96.93	63.92	1014

Literature-anchored findings (GeneRIF, showing 1)

• Identification of HAGHL as a novel metabolic oncogene regulating human colorectal cancer progression. (PMID:36417085)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Haghl	ENSMUSG00000061046
rattus_norvegicus	Haghl	ENSRNOG00000019612
drosophila_melanogaster	tzn	FBGN0037024
caenorhabditis_elegans		WBGENE00012459

Paralogs (4): HAGH (ENSG00000063854), ETHE1 (ENSG00000105755), PNKD (ENSG00000127838), MBLAC2 (ENSG00000176055)

Protein

Protein identifiers

Hydroxyacylglutathione hydrolase-like protein — Q6PII5 (reviewed: Q6PII5)

All UniProt accessions (10): Q6PII5, B4DED4, H3BN70, H3BQ57, H3BR74, H3BT20, H3BU61, I3L1B7, I3L1W0, I3L3H5

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolase acting on ester bonds.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Similarity. Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6PII5-1	1	yes
Q6PII5-2	2
Q6PII5-3	3
Q6PII5-4	4

RefSeq proteins (7): NP_001277066, NP_001277068, NP_001310564, NP_001310565, NP_001352211, NP_115680, NP_996995 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001279	Metallo-B-lactamas	Domain
IPR035680	Clx_II_MBL	Domain
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily

Pfam: PF00753

UniProt features (14 total): binding site 8, splice variant 5, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PII5-F1	77.27	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 54; 56; 58; 59; 110; 134; 134; 172

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MARTIN_VIRAL_GPCR_SIGNALING_UP, GATA1_02, SANSOM_APC_TARGETS, SANSOM_APC_TARGETS_REQUIRE_MYC, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_THIOLESTER_HYDROLASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, MARTENS_TRETINOIN_RESPONSE_DN, LU_EZH2_TARGETS_UP, LEE_BMP2_TARGETS_UP, FOSTER_KDM1A_TARGETS_DN, FOXD2_TARGET_GENES, SNRNP70_TARGET_GENES, ZNF436_TARGET_GENES

GO Biological Process (1): obsolete methylglyoxal catabolic process to pyruvate via (R)-S-lactoyl-glutathione (GO:0019243)

GO Molecular Function (4): hydroxyacylglutathione hydrolase activity (GO:0004416), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
thiolester hydrolase activity	1
cation binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

1360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HAGHL	LACTB2	Q53H82	544
HAGHL	MBLAC2	Q68D91	507
HAGHL	MBLAC1	A4D2B0	497
HAGHL	C1orf174	Q8IYL3	447
HAGHL	PRR29	P0C7W0	447
HAGHL	GLO1	P78375	440
HAGHL	TMEM254	Q8TBM7	370
HAGHL	MROH6	A6NGR9	369
HAGHL	CSRNP2	Q9H175	355
HAGHL	DCST2	Q5T1A1	355
HAGHL	PDCD2L	Q9BRP1	354
HAGHL	SUOX	P51687	353
HAGHL	CCDC167	Q9P0B6	351
HAGHL	PPP1R2C	O14990	350
HAGHL	SPANXN1	Q5VSR9	348

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CSNK2A2	EIF3J	psi-mi:“MI:0914”(association)	0.790
CSNK2A2	PES1	psi-mi:“MI:0914”(association)	0.640
HAGHL		psi-mi:“MI:0915”(physical association)	0.560
HAGHL	FKBP1A	psi-mi:“MI:0915”(physical association)	0.560
TM4SF1	HAGHL	psi-mi:“MI:0915”(physical association)	0.560
HAGHL	PMP22	psi-mi:“MI:0915”(physical association)	0.560
HAGHL	C5AR2	psi-mi:“MI:0915”(physical association)	0.370
CSNK2A2	SAP18	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): HAGHL (Affinity Capture-MS), HAGHL (Synthetic Growth Defect), HAGHL (Affinity Capture-MS), HAGHL (Two-hybrid), HAGHL (Affinity Capture-MS), HAGHL (Affinity Capture-MS), HAGHL (Affinity Capture-MS), HAGHL (Affinity Capture-MS), HAGHL (Affinity Capture-MS), HAGHL (Affinity Capture-RNA), HAGHL (Affinity Capture-MS)

ESM2 similar proteins: A5PJT0, D2H8V8, F7E727, I3L5V6, O02785, O33821, O43304, O43598, O68638, O75808, O88816, O97756, P07760, P25908, P51656, P51657, P79774, Q0VBY3, Q16613, Q29495, Q48412, Q4KLY6, Q59750, Q5EDC3, Q5F336, Q5IS55, Q5QJC3, Q5ZLY2, Q60806, Q64666, Q68D91, Q6PDS3, Q6PII5, Q7Z5J1, Q80VJ3, Q89TZ6, Q8BL86, Q8BZL1, Q8C1R0, Q8C262

Diamond homologs: A0A067XMV3, A0A1L9WLF1, A0A2I1C3U0, A0A411PQM3, A0A4P8DJU1, A0A5B8YUX5, A0A7R7ZLL0, A0KIK2, A1D8J2, A1JKA9, A1S6T3, A1WXD9, A2QX23, A3MZD3, A4SPI6, A4TL56, A5ETG1, A5GJK5, A7FFK5, A7MI37, A7Z4X7, B0BTR9, B0TXY0, B0U365, B1JR44, B2I5S5, B2KAD1, B2VHJ7, B3H0S9, B5F9V3, B7VIP5, C5FM60, D4AWH0, D4CZZ5, D7PHZ8, E1ACR1, E4V2N5, F2PWS8, F2S702, F2T0M3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

79 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2025 predictions. Top by Δscore:

Variant	Effect	Δscore
16:727611:GAGG:G	donor_gain	1.0000
16:727613:GG:G	donor_gain	1.0000
16:727614:GG:G	donor_gain	1.0000
16:728111:CGCAG:C	acceptor_loss	1.0000
16:728112:GCAGG:G	acceptor_loss	1.0000
16:728113:CAGGG:C	acceptor_loss	1.0000
16:728114:A:AT	acceptor_loss	1.0000
16:728114:AG:A	acceptor_gain	1.0000
16:728115:GG:G	acceptor_gain	1.0000
16:728230:GCGG:G	donor_gain	1.0000
16:728231:CGGG:C	donor_loss	1.0000
16:728232:GG:G	donor_gain	1.0000
16:728233:GG:G	donor_gain	1.0000
16:728233:GGTGA:G	donor_loss	1.0000
16:728234:G:GA	donor_loss	1.0000
16:728234:G:GG	donor_gain	1.0000
16:728235:T:G	donor_loss	1.0000
16:728581:C:G	donor_gain	1.0000
16:728793:GAA:G	acceptor_gain	1.0000
16:728869:G:GG	donor_gain	1.0000
16:728889:GGC:G	donor_gain	1.0000
16:728890:GC:G	donor_gain	1.0000
16:728891:C:G	donor_gain	1.0000
16:728997:T:TA	acceptor_gain	1.0000
16:729002:A:AG	acceptor_gain	1.0000
16:729007:A:AG	acceptor_gain	1.0000
16:729008:G:GG	acceptor_gain	1.0000
16:729008:GAA:G	acceptor_gain	1.0000
16:729084:GTGGC:G	donor_gain	1.0000
16:729089:G:GG	donor_gain	1.0000

AlphaMissense

1808 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:728800:T:C	F169L	0.993
16:728802:C:A	F169L	0.993
16:728802:C:G	F169L	0.993
16:728836:T:C	F181L	0.993
16:728838:T:A	F181L	0.993
16:728838:T:G	F181L	0.993
16:727589:C:A	A27D	0.991
16:728419:T:C	F131S	0.990
16:728418:T:C	F131L	0.986
16:728420:C:A	F131L	0.986
16:728420:C:G	F131L	0.986
16:727552:T:G	Y15D	0.985
16:727559:T:A	V17D	0.985
16:728339:C:G	C104W	0.985
16:728373:A:C	S116R	0.985
16:728375:C:A	S116R	0.985
16:728375:C:G	S116R	0.985
16:727526:T:C	I6T	0.984
16:727556:T:C	L16P	0.984
16:727582:G:C	A25P	0.983
16:727594:G:C	D29H	0.982
16:728337:T:C	C104R	0.982
16:727595:A:T	D29V	0.980
16:728017:C:T	T53I	0.980
16:728376:T:G	Y117D	0.979
16:727517:T:A	V3D	0.978
16:727596:C:A	D29E	0.976
16:727596:C:G	D29E	0.976
16:728801:T:C	F169S	0.976
16:727552:T:C	Y15H	0.975

dbSNP variants (sampled 300 via entrez): RS1000398460 (16:730102 G>A), RS1000580272 (16:725314 G>A,C), RS1000769425 (16:729928 C>A,G,T), RS1000982054 (16:729804 G>A), RS1001010041 (16:729924 AC>A,ACC,ACCC,ACCCC), RS1001573428 (16:727921 G>T), RS1001820836 (16:729673 G>A,C), RS1001836787 (16:726753 G>A,T), RS1001939682 (16:727761 G>A,C), RS1002536785 (16:728767 C>A,G,T), RS1002884761 (16:728349 C>T), RS1002917360 (16:728719 G>A,C), RS1004345653 (16:726480 C>A,T), RS1004872968 (16:728280 C>A,T), RS1004883206 (16:729535 T>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST008163_25	Height	4.000000e-06
GCST008839_213	Height	9.000000e-08
GCST011110_1	First fracture in long-term childhood cancer survivors (time to event)	8.000000e-09
GCST012226_129	Waist circumference adjusted for body mass index	1.000000e-10
GCST012226_378	Waist circumference adjusted for body mass index	7.000000e-15
GCST012227_358	Hip circumference adjusted for BMI	8.000000e-21
GCST012227_359	Hip circumference adjusted for BMI	8.000000e-09
GCST90020028_1482	Hip circumference adjusted for BMI	3.000000e-12
GCST90020028_1483	Hip circumference adjusted for BMI	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, increases methylation	2
TAK-243	increases sumoylation	1
sodium arsenite	decreases expression	1
zinc chromate	increases abundance, increases expression	1
1-hydroxypyrene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
jinfukang	increases expression	1
prothioconazole	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.