ASPHD1

Summary

ASPHD1 (aspartate beta-hydroxylase domain containing 1, HGNC:27380) is a protein-coding gene on chromosome 16p11.2, encoding Aspartate beta-hydroxylase domain-containing protein 1 (Q5U4P2).

Predicted to enable dioxygenase activity. Predicted to be located in membrane.

Source: NCBI Gene 253982 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 92 total — 3 pathogenic
• MANE Select transcript: NM_181718

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27380
Approved symbol	ASPHD1
Name	aspartate beta-hydroxylase domain containing 1
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174939
Ensembl biotype	protein_coding
Entrez	253982

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

ENST00000308748, ENST00000414952, ENST00000483405, ENST00000563177, ENST00000566693, ENST00000651383, ENST00000867089

RefSeq mRNA: 1 — MANE Select: NM_181718 NM_181718

CCDS: CCDS10660

Canonical transcript exons

ENST00000308748 — 3 exons

Exon	Start	End
ENSE00001178606	29904852	29904965
ENSE00001301953	29900488	29901920
ENSE00001902509	29905788	29906056

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5653 / max 122.0639, expressed in 1336 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153558	5.3004	1271
153559	1.2648	455

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.70	gold quality
putamen	UBERON:0001874	97.56	gold quality
right frontal lobe	UBERON:0002810	97.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.32	gold quality
nucleus accumbens	UBERON:0001882	97.00	gold quality
caudate nucleus	UBERON:0001873	96.96	gold quality
cerebellar hemisphere	UBERON:0002245	96.87	gold quality
amygdala	UBERON:0001876	96.79	gold quality
cerebellar cortex	UBERON:0002129	96.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.63	gold quality
prefrontal cortex	UBERON:0000451	96.61	gold quality
cerebellum	UBERON:0002037	95.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.50	gold quality
spinal cord	UBERON:0002240	95.37	gold quality
cingulate cortex	UBERON:0003027	94.96	gold quality
Ammon’s horn	UBERON:0001954	94.87	gold quality
anterior cingulate cortex	UBERON:0009835	94.74	gold quality
temporal lobe	UBERON:0001871	94.15	gold quality
telencephalon	UBERON:0001893	94.10	gold quality
substantia nigra	UBERON:0002038	93.67	gold quality
forebrain	UBERON:0001890	93.61	gold quality
frontal cortex	UBERON:0001870	93.57	gold quality
central nervous system	UBERON:0001017	93.54	gold quality
brain	UBERON:0000955	93.51	gold quality
cerebral cortex	UBERON:0000956	93.21	gold quality
neocortex	UBERON:0001950	93.11	gold quality
postcentral gyrus	UBERON:0002581	93.10	gold quality
midbrain	UBERON:0001891	92.90	gold quality
parietal lobe	UBERON:0001872	92.80	gold quality
superior frontal gyrus	UBERON:0002661	91.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting ASPHD1, 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-4455	100.00	65.48	1587
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-892C-5P	99.16	70.56	2116

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	asphd1	ENSDARG00000075813
mus_musculus	Asphd1	ENSMUSG00000046378
rattus_norvegicus	Asphd1	ENSRNOG00000027213
drosophila_melanogaster	Asph	FBGN0034075
caenorhabditis_elegans		WBGENE00010703

Paralogs (2): ASPHD2 (ENSG00000128203), ASPH (ENSG00000198363)

Protein

Protein identifiers

Aspartate beta-hydroxylase domain-containing protein 1 — Q5U4P2 (reviewed: Q5U4P2)

All UniProt accessions (3): Q5U4P2, I3L2A5, I3L2Y2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

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

RefSeq proteins (1): NP_859069* (*=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 (10 total): topological domain 2, region of interest 2, compositionally biased region 2, chain 1, transmembrane region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5U4P2-F1	76.01	0.52

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 (1): 129

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, ATF_B, RNGTGGGC_UNKNOWN, SP3_Q3, CREBP1_Q2, GGGTGGRR_PAX4_03, CREB_Q4, ATF1_Q6, GATA6_01, chr16p11, E4F1_Q6, CREB_Q2_01, SCHLOSSER_SERUM_RESPONSE_DN, RGAGGAARY_PU1_Q6, HAMAI_APOPTOSIS_VIA_TRAIL_DN

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

GO Molecular Function (2): dioxygenase activity (GO:0051213), 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
oxidoreductase activity	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASPHD1	KCTD13	Q8WZ19	810
ASPHD1	C16orf54	Q6UWD8	804
ASPHD1	SEZ6L2	Q6UXD5	796
ASPHD1	CDIPT	O14735	698
ASPHD1	HIRIP3	Q9BW71	688
ASPHD1	YPEL3	P61236	687
ASPHD1	FIMP1	Q96LL3	680
ASPHD1	DOC2A	Q14183	673
ASPHD1	INO80E	Q8NBZ0	667
ASPHD1	KIF22	Q14807	653
ASPHD1	TMEM219	Q86XT9	632
ASPHD1	PAGR1	Q9BTK6	632
ASPHD1	TLCD3B	Q71RH2	605
ASPHD1	C1orf94	Q6P1W5	602
ASPHD1	TAOK2	Q9UL54	590

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ASPHD1	POMP	psi-mi:“MI:0915”(physical association)	0.400
ASPHD1	TSHR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (6): ASPHD1 (Biochemical Activity), ASPHD1 (Two-hybrid), ASPHD1 (Affinity Capture-RNA), POMP (Affinity Capture-MS), ASPHD1 (Reconstituted Complex), ASPHD1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0U1RR11, A0A0U1RRI6, A6NCS6, A6NJG2, B0BN44, D3YXK1, E9PY61, E9Q0B3, F5H4A9, O00220, O00221, P09038, P0DPI3, P22083, P98077, Q08AU9, Q2M2W7, Q2M3V2, Q2TBI2, Q5F267, Q5FW56, Q5IS69, Q5R866, Q5T4W7, Q5TM52, Q5U4P2, Q5VTJ3, Q659K9, Q673H1, Q69ZB3, Q6AYE8, Q6IPT2, Q6PJ61, Q7RTU4, Q7TSX9, Q7YR31, Q80SU3, Q86SH2, Q86Y97, Q8NBR0

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	78
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2685569	GRCh37/hg19 16p11.2(chr16:29383809-29957798)x1	Pathogenic
584215	NC_000016.10:g.(?29813055)(29904965_?)del	Pathogenic
625608	GRCh37/hg19 16p11.2(chr16:29727054-29969912)	Pathogenic

SpliceAI

1299 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29910972:TCTGA:T	donor_loss	1.0000
16:29910973:CTGAC:C	donor_loss	1.0000
16:29910974:TGAC:T	donor_loss	1.0000
16:29910975:GACCT:G	donor_loss	1.0000
16:29910976:ACCT:A	donor_loss	1.0000
16:29910977:C:T	donor_loss	1.0000
16:29911182:C:CT	acceptor_gain	1.0000
16:29911183:A:T	acceptor_gain	1.0000
16:29911864:CGGG:C	acceptor_gain	1.0000
16:29911868:C:CC	acceptor_gain	1.0000
16:29911954:CCTCA:C	donor_loss	1.0000
16:29911955:CTCA:C	donor_loss	1.0000
16:29911956:TCACC:T	donor_loss	1.0000
16:29911957:CACCT:C	donor_loss	1.0000
16:29911958:ACCT:A	donor_loss	1.0000
16:29911959:C:CA	donor_loss	1.0000
16:29912045:TTTTG:T	acceptor_gain	1.0000
16:29912046:TTTG:T	acceptor_gain	1.0000
16:29912047:TTG:T	acceptor_gain	1.0000
16:29912050:C:CA	acceptor_loss	1.0000
16:29912050:C:CC	acceptor_gain	1.0000
16:29901919:GG:G	donor_gain	0.9900
16:29901920:GG:G	donor_gain	0.9900
16:29911171:GTG:G	acceptor_gain	0.9900
16:29911172:TG:T	acceptor_gain	0.9900
16:29911173:GCTGG:G	acceptor_loss	0.9900
16:29911174:C:A	acceptor_loss	0.9900
16:29911174:C:CC	acceptor_gain	0.9900
16:29911182:C:T	acceptor_gain	0.9900
16:29911872:C:CT	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000236584 (16:29910828 G>C,T), RS1000360762 (16:29900402 G>A,T), RS1000588711 (16:29910486 T>C,G), RS1000693028 (16:29903891 C>A,T), RS1000984083 (16:29900259 C>A), RS1001263469 (16:29917513 G>A), RS1001520761 (16:29903958 C>T), RS1001577892 (16:29904339 G>A), RS1001612164 (16:29912334 C>T), RS1002015002 (16:29907221 T>C), RS1002047430 (16:29907632 C>CA), RS1002212534 (16:29911463 G>A), RS1002213299 (16:29913452 G>A), RS1002270795 (16:29915982 C>T), RS1002297583 (16:29901085 C>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:128200, MIM:614671

GenCC curated gene-disease

Mondo (3): primary ovarian failure (MONDO:0005387), episodic kinesigenic dyskinesia (MONDO:0044202), chromosome 16p11.2 duplication syndrome (MONDO:0013847)

Orphanet (3): Paroxysmal kinesigenic dyskinesia (Orphanet:98809), Proximal 16p11.2 microduplication syndrome (Orphanet:370079), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002539_82	Schizophrenia	5.000000e-11
GCST004521_236	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST004946_142	Schizophrenia	8.000000e-13
GCST006803_23	Schizophrenia	6.000000e-13
GCST007293_15	Body fat distribution (arm fat ratio)	6.000000e-06
GCST007293_81	Body fat distribution (arm fat ratio)	4.000000e-08
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
dicrotophos	decreases expression	1
beta-lapachone	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Arsenic	increases methylation	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Quercetin	increases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists