HDHD3

Summary

HDHD3 (haloacid dehalogenase like hydrolase domain containing 3, HGNC:28171) is a protein-coding gene on chromosome 9q32, encoding Haloacid dehalogenase-like hydrolase domain-containing protein 3 (Q9BSH5).

Predicted to enable hydrolase activity. Located in nucleolus.

Source: NCBI Gene 81932 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_001304509

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28171
Approved symbol	HDHD3
Name	haloacid dehalogenase like hydrolase domain containing 3
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	MGC12904
Ensembl gene	ENSG00000119431
Ensembl biotype	protein_coding
Entrez	81932

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000238379, ENST00000374180, ENST00000485934, ENST00000900262, ENST00000900263, ENST00000900264, ENST00000900265, ENST00000900266, ENST00000900267, ENST00000900268, ENST00000900269, ENST00000900270, ENST00000900271, ENST00000928135, ENST00000968238, ENST00000968239

RefSeq mRNA: 5 — MANE Select: NM_001304509 NM_001304509, NM_001304510, NM_001304511, NM_001371923, NM_031219

CCDS: CCDS6793

Canonical transcript exons

ENST00000374180 — 3 exons

Exon	Start	End
ENSE00001462712	113375453	113375567
ENSE00001872572	113376729	113376986
ENSE00003916062	113373422	113374529

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4079 / max 162.4997, expressed in 1732 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102099	8.2004	1703
102098	3.2075	1192

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	98.67	gold quality
right adrenal gland cortex	UBERON:0035827	98.55	gold quality
left adrenal gland	UBERON:0001234	98.13	gold quality
mucosa of transverse colon	UBERON:0004991	98.10	gold quality
left adrenal gland cortex	UBERON:0035825	98.02	gold quality
adrenal cortex	UBERON:0001235	97.21	gold quality
adrenal gland	UBERON:0002369	96.27	gold quality
right lobe of liver	UBERON:0001114	95.71	gold quality
transverse colon	UBERON:0001157	94.30	gold quality
duodenum	UBERON:0002114	93.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.75	gold quality
ileal mucosa	UBERON:0000331	93.71	gold quality
jejunal mucosa	UBERON:0000399	93.41	gold quality
body of pancreas	UBERON:0001150	93.38	gold quality
right lobe of thyroid gland	UBERON:0001119	93.22	gold quality
body of stomach	UBERON:0001161	93.20	gold quality
small intestine	UBERON:0002108	92.55	gold quality
left lobe of thyroid gland	UBERON:0001120	92.18	gold quality
apex of heart	UBERON:0002098	91.89	gold quality
metanephros cortex	UBERON:0010533	91.70	gold quality
esophagus mucosa	UBERON:0002469	91.63	gold quality
rectum	UBERON:0001052	91.39	gold quality
minor salivary gland	UBERON:0001830	90.96	gold quality
adrenal tissue	UBERON:0018303	90.84	gold quality
thyroid gland	UBERON:0002046	90.83	gold quality
saliva-secreting gland	UBERON:0001044	90.69	gold quality
lower esophagus mucosa	UBERON:0035834	90.62	gold quality
intestine	UBERON:0000160	90.05	gold quality
stomach	UBERON:0000945	89.77	gold quality
adult mammalian kidney	UBERON:0000082	89.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	111.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting HDHD3, 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-4531	99.99	69.70	3181
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4665-5P	97.91	67.69	1536

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdhd3	ENSDARG00000053934
mus_musculus	Hdhd3	ENSMUSG00000038422
rattus_norvegicus	Hdhd3	ENSRNOG00000064638
drosophila_melanogaster	Reg-2	FBGN0016715
drosophila_melanogaster	CG15912	FBGN0029712
caenorhabditis_elegans		WBGENE00010481

Paralogs (1): NANP (ENSG00000170191)

Protein

Protein identifiers

Haloacid dehalogenase-like hydrolase domain-containing protein 3 — Q9BSH5 (reviewed: Q9BSH5)

All UniProt accessions (1): Q9BSH5

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the HAD-like hydrolase superfamily.

RefSeq proteins (5): NP_001291438, NP_001291439, NP_001291440, NP_001358852, NP_112496 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006439	HAD-SF_hydro_IA	Family
IPR011949	HAD-SF_hydro_IA_REG-2-like	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR044924	HAD-SF_hydro_IA_REG-2-like_cap	Homologous_superfamily
IPR051828	HAD-like_hydrolase_domain	Family

Pfam: PF00702

UniProt features (32 total): helix 18, strand 8, modified residue 2, turn 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3K1Z	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSH5-F1	95.84	0.96

Functional residue map

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

Post-translational modifications (2): 15, 15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, BONOME_OVARIAN_CANCER_POOR_SURVIVAL_DN, TGGAAA_NFAT_Q4_01, GOCC_NUCLEOLUS, BONOME_OVARIAN_CANCER_SURVIVAL_SUBOPTIMAL_DEBULKING, LIM_MAMMARY_STEM_CELL_DN, ZWANG_DOWN_BY_2ND_EGF_PULSE, SUPT16H_TARGET_GENES, GSE10325_BCELL_VS_MYELOID_UP, GSE11924_TFH_VS_TH17_CD4_TCELL_DN, GSE12845_NAIVE_VS_PRE_GC_TONSIL_BCELL_UP, GSE14308_TH1_VS_NAIVE_CD4_TCELL_UP, GSE17721_PAM3CSK4_VS_CPG_2H_BMDC_UP, AIZARANI_LIVER_C30_HEPATOCYTES_4, MURARO_PANCREAS_DUCTAL_CELL

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleolus (GO:0005730), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1327 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDHD3	TSPEAR	Q8WU66	513
HDHD3	C10orf120	Q5SQS8	505
HDHD3	AGAP5	A6NIR3	475
HDHD3	FGFBP3	Q8TAT2	469
HDHD3	NDRG3	Q9UGV2	458
HDHD3	POLR3E	Q9NVU0	430
HDHD3	OR10A2	Q9H208	417
HDHD3	INTS7	Q9NVH2	401
HDHD3	CCDC137	Q6PK04	394
HDHD3	B4GALT3	O60512	386
HDHD3	SUPT3H	O75486	383
HDHD3	CALHM3	Q86XJ0	365
HDHD3	NIF3L1	Q9GZT8	365
HDHD3	SNRPA1	P09661	361
HDHD3	EMC8	O43402	357

IntAct

50 interactions, top by confidence:

A	B	Type	Score
TRIP13	HDHD3	psi-mi:“MI:0915”(physical association)	0.760
HDHD3	MTHFD2L	psi-mi:“MI:0915”(physical association)	0.590
VAC14	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
KLHL38	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
ATG9A	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
HDHD3	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
HDHD3	FANCL	psi-mi:“MI:0915”(physical association)	0.560
TLE5	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
SMYD1	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
PROP1	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	HDHD3	psi-mi:“MI:0915”(physical association)	0.560
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
C19orf25	NBAS	psi-mi:“MI:0914”(association)	0.350
MTPN	PLCG1	psi-mi:“MI:0914”(association)	0.350
HDHD3	PCCA	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
HDHD3	TRIP13	psi-mi:“MI:0915”(physical association)	0.000
HDHD3	VAC14	psi-mi:“MI:0915”(physical association)	0.000
KLHL38	HDHD3	psi-mi:“MI:0915”(physical association)	0.000
ATG9A	HDHD3	psi-mi:“MI:0915”(physical association)	0.000
POU4F2	HDHD3	psi-mi:“MI:0915”(physical association)	0.000
CSTF2	HDHD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): HDHD3 (Affinity Capture-RNA), HDHD3 (Two-hybrid), PITRM1 (Co-fractionation), MTHFD2L (Affinity Capture-MS), HDHD3 (Affinity Capture-MS), HDHD3 (Affinity Capture-MS), HDHD3 (Co-fractionation), HDHD3 (Co-fractionation), HDHD3 (Co-fractionation), NENF (Co-fractionation), HDHD3 (Co-fractionation), HDHD3 (Co-fractionation), POLDIP2 (Co-fractionation), HDHD3 (Co-fractionation), HDHD3 (Co-fractionation)

ESM2 similar proteins: A0JNU3, A1A4L8, A2BDX3, A5GFZ6, A6NK58, A6QQ74, O19179, O43542, O60294, O95336, O95396, P19971, P85971, Q02846, Q05922, Q08DH8, Q0VFH3, Q28F19, Q29R99, Q2TBQ8, Q2V057, Q3SZ07, Q3UQ84, Q561R2, Q5ZKI2, Q68FW7, Q6PAT0, Q6QHF9, Q86U10, Q86WU2, Q86Y79, Q8BW00, Q8IVS8, Q8N8Q3, Q8R123, Q8VCZ9, Q8VDG5, Q8WV74, Q8WVB3, Q8WZ82

Diamond homologs: A0RKU8, A9VQ75, B7HEG2, B7IPS5, B7JFI8, C1EZE2, C3LED0, C3P0C8, F8D9F4, O26311, O32125, O59346, P44755, P94512, Q2UEK4, Q3B8E3, Q3UGR5, Q3ZCH9, Q4QMY0, Q58832, Q5BJJ5, Q5E9D6, Q5R4B4, Q631J2, Q6AYR6, Q6HBC8, Q6HQY9, Q72H00, Q72XV8, Q815I8, Q8TWR2, Q8U040, Q9BSH5, Q9CKJ5, Q9CYW4, Q9H0R4, Q9V1B3, Q08CY5, Q5HZL9, Q7T012

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

199 predictions. Top by Δscore:

Variant	Effect	Δscore
9:113374528:TC:T	acceptor_gain	0.9800
9:113374529:CC:C	acceptor_gain	0.9800
9:113375723:AG:A	donor_gain	0.9800
9:113374531:T:A	acceptor_loss	0.9700
9:113375447:ACTT:A	donor_loss	0.9700
9:113375448:CTT:C	donor_loss	0.9700
9:113375449:TTAC:T	donor_loss	0.9700
9:113375450:TACCC:T	donor_loss	0.9700
9:113375451:AC:A	donor_gain	0.9600
9:113375452:CC:C	donor_gain	0.9600
9:113375452:CCCAA:C	donor_gain	0.9600
9:113374530:C:CC	acceptor_gain	0.9500
9:113375724:G:C	donor_gain	0.9500
9:113375445:GTACT:G	donor_loss	0.9300
9:113375446:TACTT:T	donor_loss	0.9300
9:113375527:C:CC	acceptor_gain	0.9200
9:113375451:A:AC	donor_gain	0.9100
9:113375452:C:CC	donor_gain	0.9100
9:113374526:GATC:G	acceptor_gain	0.9000
9:113375840:G:C	donor_gain	0.9000
9:113375452:CCCA:C	donor_gain	0.8800
9:113375533:C:CT	acceptor_gain	0.8800
9:113375839:A:AC	donor_gain	0.8800
9:113376131:A:AC	donor_gain	0.8700
9:113376132:C:CC	donor_gain	0.8700
9:113375451:ACC:A	donor_gain	0.8500
9:113375452:CCC:C	donor_gain	0.8500
9:113376044:CGG:C	donor_gain	0.8200
9:113376133:TGC:T	donor_gain	0.8000
9:113374525:AGATC:A	acceptor_gain	0.7900

AlphaMissense

1610 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:113373854:C:A	K167N	0.990
9:113373854:C:G	K167N	0.990
9:113373836:G:C	F173L	0.985
9:113373836:G:T	F173L	0.985
9:113373838:A:G	F173L	0.985
9:113373947:G:C	N136K	0.985
9:113373947:G:T	N136K	0.985
9:113374317:T:A	D13V	0.985
9:113373944:A:C	F137L	0.984
9:113373944:A:T	F137L	0.984
9:113373946:A:G	F137L	0.984
9:113373942:T:A	D138V	0.983
9:113373951:G:A	S135F	0.982
9:113374316:A:C	D13E	0.982
9:113374316:A:T	D13E	0.982
9:113373855:T:G	K167T	0.979
9:113374317:T:G	D13A	0.979
9:113373765:T:A	D197V	0.976
9:113373783:C:A	G191V	0.973
9:113374208:G:C	F49L	0.972
9:113374208:G:T	F49L	0.972
9:113374210:A:G	F49L	0.972
9:113373786:A:T	V190D	0.971
9:113373856:T:C	K167E	0.971
9:113374024:A:G	W111R	0.971
9:113374024:A:T	W111R	0.971
9:113373764:A:C	D197E	0.970
9:113373764:A:T	D197E	0.970
9:113373765:T:G	D197A	0.970
9:113373951:G:T	S135Y	0.969

dbSNP variants (sampled 300 via entrez): RS1000132984 (9:113378062 C>G,T), RS1000673165 (9:113375383 T>C,G), RS1001221457 (9:113378351 G>A), RS1001260328 (9:113377684 C>G,T), RS1001296433 (9:113372978 G>A), RS1001878777 (9:113378573 A>T), RS1002016833 (9:113378145 A>C,G), RS1002297241 (9:113377985 A>G), RS1002344895 (9:113378937 C>A), RS1003304750 (9:113377043 C>G,T), RS1004129786 (9:113378872 C>T), RS1004160564 (9:113372924 G>A), RS1005219840 (9:113373079 T>C), RS1005240119 (9:113375990 G>T), RS1005329819 (9:113378834 G>C,T)

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

2 associations (top):

Study	Trait	p-value
GCST009391_1416	Metabolite levels	9.000000e-06
GCST010396_215	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010451	aconitate measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
GSK-J4	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	decreases response to substance	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	increases methylation	1
Atrazine	increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Lead	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Vincristine	decreases expression	1
Gold Compounds	increases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SR24	HAP1 HDHD3 (-) 1	Cancer cell line	Male
CVCL_XP46	HAP1 HDHD3 (-) 2	Cancer cell line	Male
CVCL_XP47	HAP1 HDHD3 (-) 3	Cancer cell line	Male
CVCL_XP48	HAP1 HDHD3 (-) 4	Cancer cell line	Male
CVCL_XP49	HAP1 HDHD3 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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