ASPHD2

Summary

ASPHD2 (aspartate beta-hydroxylase domain containing 2, HGNC:30437) is a protein-coding gene on chromosome 22q12.1, encoding Aspartate beta-hydroxylase domain-containing protein 2 (Q6ICH7). May function as 2-oxoglutarate-dependent dioxygenase.

Predicted to enable dioxygenase activity and metal ion binding activity. Located in membrane.

Source: NCBI Gene 57168 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_020437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30437
Approved symbol	ASPHD2
Name	aspartate beta-hydroxylase domain containing 2
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ39838
Ensembl gene	ENSG00000128203
Ensembl biotype	protein_coding
Entrez	57168

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000215906, ENST00000851348, ENST00000851349, ENST00000924146, ENST00000924147, ENST00000924148, ENST00000953700, ENST00000953701

RefSeq mRNA: 1 — MANE Select: NM_020437 NM_020437

CCDS: CCDS13834

Canonical transcript exons

ENST00000215906 — 4 exons

Exon	Start	End
ENSE00000651875	26433392	26434501
ENSE00000651876	26442459	26442572
ENSE00001836395	26443097	26445015
ENSE00001889956	26429260	26429486

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 91.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.8778 / max 80.3897, expressed in 1094 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191505	2.8778	1094

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	91.06	gold quality
middle temporal gyrus	UBERON:0002771	90.88	gold quality
pancreatic ductal cell	CL:0002079	88.75	silver quality
Brodmann (1909) area 23	UBERON:0013554	88.04	gold quality
endothelial cell	CL:0000115	86.59	gold quality
primary visual cortex	UBERON:0002436	84.81	gold quality
cerebellar cortex	UBERON:0002129	84.48	gold quality
cerebellar hemisphere	UBERON:0002245	84.47	gold quality
cerebellum	UBERON:0002037	84.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.67	gold quality
nucleus accumbens	UBERON:0001882	83.67	gold quality
cerebellar vermis	UBERON:0004720	83.34	gold quality
entorhinal cortex	UBERON:0002728	83.07	gold quality
cortical plate	UBERON:0005343	82.08	gold quality
putamen	UBERON:0001874	82.04	gold quality
caudate nucleus	UBERON:0001873	81.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.59	gold quality
prefrontal cortex	UBERON:0000451	81.47	gold quality
sperm	CL:0000019	80.53	gold quality
oocyte	CL:0000023	80.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.62	gold quality
occipital lobe	UBERON:0002021	79.61	gold quality
frontal cortex	UBERON:0001870	79.40	gold quality
monocyte	CL:0000576	78.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.96	gold quality
leukocyte	CL:0000738	78.94	gold quality
superior frontal gyrus	UBERON:0002661	78.94	gold quality
neocortex	UBERON:0001950	78.70	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting ASPHD2, 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-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-587	99.64	70.86	2611

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	asphd2	ENSDARG00000059629
mus_musculus	Asphd2	ENSMUSG00000029348
rattus_norvegicus	Asphd2	ENSRNOG00000061004
drosophila_melanogaster	Asph	FBGN0034075
caenorhabditis_elegans		WBGENE00010703

Paralogs (2): ASPHD1 (ENSG00000174939), ASPH (ENSG00000198363)

Protein

Protein identifiers

Aspartate beta-hydroxylase domain-containing protein 2 — Q6ICH7 (reviewed: Q6ICH7)

All UniProt accessions (1): Q6ICH7

UniProt curated annotations — full annotation on UniProt →

Function. May function as 2-oxoglutarate-dependent dioxygenase.

Subcellular location. Membrane.

Similarity. Belongs to the aspartyl/asparaginyl beta-hydroxylase family.

RefSeq proteins (1): NP_065170* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007803	Asp/Arg/Pro-Hydrxlase	Domain
IPR027443	IPNS-like_sf	Homologous_superfamily
IPR051821	Asp/Asn_beta-hydroxylase	Family

Pfam: PF05118

UniProt features (12 total): binding site 6, topological domain 2, chain 1, glycosylation site 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ICH7-F1	81.08	0.63

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 (6): 228; 272; 283; 292–294; 328; 341

Glycosylation sites (1): 211

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, MODULE_205, RIGGI_EWING_SARCOMA_PROGENITOR_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_DIOXYGENASE_ACTIVITY, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, WHITFIELD_CELL_CYCLE_G2_M, WAMUNYOKOLI_OVARIAN_CANCER_GRADES_1_2_UP, ANDERSEN_CHOLANGIOCARCINOMA_CLASS2, RATTENBACHER_BOUND_BY_CELF1, LIM_MAMMARY_STEM_CELL_UP, RYBP_TARGET_GENES, CASP8AP2_TARGET_GENES

GO Biological Process (1): peptidyl-amino acid modification (GO:0018193)

GO Molecular Function (4): metal ion binding (GO:0046872), dioxygenase activity (GO:0051213), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification process	1
cation binding	1
oxidoreductase activity	1
binding	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASPHD2	SRRD	Q9UH36	636
ASPHD2	TMEM53	Q6P2H8	576
ASPHD2	ACBD6	Q9BR61	526
ASPHD2	B3GLCT	Q6Y288	467
ASPHD2	HPS4	Q9NQG7	463
ASPHD2	FAM153B	P0C7A2	447
ASPHD2	ZBED8	Q8IZ13	395
ASPHD2	RBM33	Q96EV2	393
ASPHD2	AIRIM	Q9NX04	378
ASPHD2	NTPCR	Q9BSD7	376
ASPHD2	TPST2	O60704	371
ASPHD2	ZBTB40	Q9NUA8	362
ASPHD2	ASB3	Q9Y575	361
ASPHD2	DNAJC3	Q13217	359
ASPHD2	TTC33	Q6PID6	355

IntAct

74 interactions, top by confidence:

A	B	Type	Score
FAM20B	ASPHD2	psi-mi:“MI:0915”(physical association)	0.670
FAM20B	ASPHD2	psi-mi:“MI:0914”(association)	0.670
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
LYPD3	SCAMP1	psi-mi:“MI:0914”(association)	0.640
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
B4GALT3	SLC19A2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
SPRING1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
RNF170	ERLIN1	psi-mi:“MI:0914”(association)	0.530
ST3GAL2	HSPA5	psi-mi:“MI:0914”(association)	0.530
TOR1A	CLGN	psi-mi:“MI:0914”(association)	0.530
B4GALT3	ATP5MC1	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
GALNT6	B4GALT3	psi-mi:“MI:0914”(association)	0.530
CLEC2B	ASPHD2	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
TOR1A	TOR1B	psi-mi:“MI:0914”(association)	0.530

BioGRID (59): ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMH0, A2ARP1, A5PK74, A7Z050, A9JTG5, B5DE73, B5DFG1, D3YY23, D3ZU57, O00562, O35954, O43304, P0C644, P0CB42, P16386, Q01433, Q02356, Q09200, Q10468, Q32P28, Q3SZL5, Q3U308, Q3V1T4, Q4KLM6, Q5HZW3, Q5RDF1, Q5RF50, Q5U2N3, Q5ZMM1, Q68J42, Q6ICH7, Q6JHU7, Q6PD26, Q6PFW1, Q6YRM6, Q80VP9, Q86TL0, Q8BGV9, Q8BGW1, Q8CG71

Diamond homologs: A0JMH0, A1L515, B5DE73, Q12797, Q28056, Q2TA57, Q4VFY5, Q5HZW3, Q5U4P2, Q6ICH7, Q80VP9, Q8BSY0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein O-linked glycosylation via N-acetylgalactosamine	6	32.4×	1e-05
binding of sperm to zona pellucida	5	26.3×	3e-04
ERAD pathway	6	13.6×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

568 predictions. Top by Δscore:

Variant	Effect	Δscore
22:26429484:CAGG:C	donor_loss	1.0000
22:26429486:GGTAA:G	donor_loss	1.0000
22:26429488:T:A	donor_loss	1.0000
22:26442444:T:TA	acceptor_gain	1.0000
22:26442457:A:G	acceptor_gain	1.0000
22:26429483:GCAG:G	donor_gain	0.9900
22:26429487:G:GG	donor_gain	0.9900
22:26442444:T:A	acceptor_loss	0.9900
22:26442453:TACAA:T	acceptor_loss	0.9900
22:26442455:CAAG:C	acceptor_loss	0.9900
22:26442456:A:AG	acceptor_gain	0.9900
22:26442456:AAG:A	acceptor_gain	0.9900
22:26442456:AAGG:A	acceptor_loss	0.9900
22:26442457:A:C	acceptor_loss	0.9900
22:26442571:AGG:A	donor_loss	0.9900
22:26442572:GGTG:G	donor_loss	0.9900
22:26442573:GTGA:G	donor_loss	0.9900
22:26442574:T:A	donor_loss	0.9900
22:26443092:CCCA:C	acceptor_loss	0.9900
22:26443093:CCA:C	acceptor_loss	0.9900
22:26442455:C:G	acceptor_gain	0.9800
22:26442575:G:GT	donor_loss	0.9800
22:26443095:A:AG	acceptor_gain	0.9800
22:26443096:G:GG	acceptor_gain	0.9800
22:26434212:GT:G	donor_gain	0.9700
22:26442445:G:A	acceptor_gain	0.9700
22:26442454:ACAAG:A	acceptor_gain	0.9700
22:26434180:G:GT	donor_gain	0.9600
22:26442454:A:AG	acceptor_gain	0.9600
22:26442458:G:GG	acceptor_gain	0.9600

AlphaMissense

2408 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:26434267:T:A	W218R	1.000
22:26434267:T:C	W218R	1.000
22:26434479:C:A	N288K	1.000
22:26434479:C:G	N288K	1.000
22:26442512:T:A	W314R	1.000
22:26442512:T:C	W314R	1.000
22:26442546:C:T	S325F	1.000
22:26443141:T:A	W349R	1.000
22:26443141:T:C	W349R	1.000
22:26443154:T:A	V353D	1.000
22:26434004:T:C	L130P	0.999
22:26434012:T:G	Y133D	0.999
22:26434045:C:A	R144S	0.999
22:26434109:C:A	P165H	0.999
22:26434187:T:C	L191P	0.999
22:26434269:G:C	W218C	0.999
22:26434269:G:T	W218C	0.999
22:26434297:T:A	W228R	0.999
22:26434297:T:C	W228R	0.999
22:26434324:G:T	G237W	0.999
22:26434325:G:A	G237E	0.999
22:26434325:G:T	G237V	0.999
22:26434414:G:T	G267W	0.999
22:26434415:G:A	G267E	0.999
22:26434429:T:C	S272P	0.999
22:26434469:G:A	G285E	0.999
22:26434477:A:T	N288Y	0.999
22:26434478:A:T	N288I	0.999
22:26434484:G:C	R290P	0.999
22:26434492:T:C	C293R	0.999

dbSNP variants (sampled 300 via entrez): RS1000141094 (22:26434730 C>T), RS1000348336 (22:26428802 C>A), RS1000624254 (22:26435110 C>T), RS1000815 (22:26435111 A>G,T), RS1001396242 (22:26440933 AGT>A), RS1001494516 (22:26440645 G>A), RS1001838567 (22:26442218 T>C), RS1001899954 (22:26440773 G>T), RS1001904368 (22:26435893 T>C,G), RS1001935519 (22:26436223 C>T), RS1002081034 (22:26429183 G>A,C,T), RS1002301893 (22:26436521 G>A), RS1002491443 (22:26429708 G>A), RS1002543043 (22:26441872 A>G), RS1002712088 (22:26431065 C>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

2 associations (top):

Study	Trait	p-value
GCST007672_1	3-month functional outcome in ischaemic stroke (modified Rankin score)	9.000000e-06
GCST009391_900	Metabolite levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0010441	triacylglycerol 58:7 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Estradiol	decreases expression, increases expression, affects cotreatment	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, affects methylation	2
GSK-J4	decreases expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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