WDHD1

Summary

WDHD1 (WD repeat and HMG-box DNA binding protein 1, HGNC:23170) is a protein-coding gene on chromosome 14q22.2-q22.3, encoding WD repeat and HMG-box DNA-binding protein 1 (O75717). Core replisome component that acts as a replication initiation factor. It is a common-essential gene (DepMap: required in 98.3% of cancer cell lines).

The protein encoded by this gene contains multiple N-terminal WD40 domains and a C-terminal high mobility group (HMG) box. WD40 domains are found in a variety of eukaryotic proteins and may function as adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. Alternative splicing results in two transcript variants encoding different isoforms.

Source: NCBI Gene 11169 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 179 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_007086

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23170
Approved symbol	WDHD1
Name	WD repeat and HMG-box DNA binding protein 1
Location	14q22.2-q22.3
Locus type	gene with protein product
Status	Approved
Aliases	AND-1, CTF4, CHTF4
Ensembl gene	ENSG00000198554
Ensembl biotype	protein_coding
OMIM	608126
Entrez	11169

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000360586, ENST00000420358, ENST00000455555, ENST00000475379, ENST00000567693, ENST00000867024, ENST00000921951, ENST00000921952, ENST00000921953, ENST00000921954, ENST00000921955, ENST00000921956, ENST00000921957, ENST00000921958, ENST00000958252

RefSeq mRNA: 2 — MANE Select: NM_007086 NM_001008396, NM_007086

CCDS: CCDS41955, CCDS9721

Canonical transcript exons

ENST00000360586 — 26 exons

Exon	Start	End
ENSE00000572360	55007280	55007375
ENSE00000657691	54989028	54989212
ENSE00000657692	54991213	54991400
ENSE00000657694	54995603	54995813
ENSE00000657696	55000503	55000644
ENSE00000657700	55002093	55002185
ENSE00001890909	55027028	55027099
ENSE00001907538	54938949	54941690
ENSE00002585987	55000886	55000992
ENSE00003466086	55026711	55026803
ENSE00003474035	55013485	55013596
ENSE00003498073	55010309	55010460
ENSE00003502635	54957034	54957204
ENSE00003528035	54967280	54967394
ENSE00003534855	54987146	54987387
ENSE00003548040	54981540	54981696
ENSE00003574839	54955561	54955694
ENSE00003587411	54962498	54962551
ENSE00003595595	54944332	54944470
ENSE00003603601	54962738	54962853
ENSE00003609768	54966475	54966606
ENSE00003618908	54962952	54963172
ENSE00003622595	54984723	54984860
ENSE00003632615	54957592	54957635
ENSE00003653330	55008608	55008719
ENSE00003784204	55008316	55008366

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 90.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0200 / max 487.5155, expressed in 1628 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143345	11.8556	1626
143344	0.1272	66
143346	0.0373	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.50	gold quality
ventricular zone	UBERON:0003053	90.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.96	gold quality
ganglionic eminence	UBERON:0004023	85.96	gold quality
secondary oocyte	CL:0000655	83.64	gold quality
embryo	UBERON:0000922	80.47	gold quality
stromal cell of endometrium	CL:0002255	77.95	gold quality
colonic epithelium	UBERON:0000397	75.84	gold quality
mucosa of transverse colon	UBERON:0004991	75.66	gold quality
cortical plate	UBERON:0005343	75.08	gold quality
bone marrow cell	CL:0002092	75.05	gold quality
calcaneal tendon	UBERON:0003701	74.45	gold quality
rectum	UBERON:0001052	74.44	gold quality
amniotic fluid	UBERON:0000173	73.87	gold quality
esophagus mucosa	UBERON:0002469	71.90	gold quality
adrenal tissue	UBERON:0018303	71.90	gold quality
bone marrow	UBERON:0002371	71.86	gold quality
testis	UBERON:0000473	71.58	gold quality
vermiform appendix	UBERON:0001154	71.25	gold quality
right testis	UBERON:0004534	70.94	gold quality
islet of Langerhans	UBERON:0000006	70.36	gold quality
left testis	UBERON:0004533	70.06	gold quality
lymph node	UBERON:0000029	69.44	gold quality
smooth muscle tissue	UBERON:0001135	69.01	gold quality
granulocyte	CL:0000094	68.55	gold quality
lower esophagus mucosa	UBERON:0035834	68.43	gold quality
skin of abdomen	UBERON:0001416	67.99	gold quality
skin of leg	UBERON:0001511	67.92	gold quality
tonsil	UBERON:0002372	67.78	gold quality
esophagus	UBERON:0001043	67.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting WDHD1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-548D-3P	99.87	70.67	4362

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 22)

• Mcm10 is required for chromatin loading of And-1. (PMID:17761813)
• AND-1 coordinates multiple cellular events in S phase and G2 phase. (PMID:19439411)
• Assembly of the Cdc45-Mcm2-7-GINS complex requires the Ctf4/And-1, RecQL4, and Mcm10 proteins. (PMID:19805216)
• in human cells, hCtf4 plays an essential role in DNA replication and its ability to stimulate the replicative DNA polymerases may contribute to this effect (PMID:20089864)
• Data show that And-1 forms a complex with both histone H3 and Gcn5. (PMID:21725360)
• Human And-1 facilitates loading of the MCM2-7 helicase onto chromatin during the assembly of prereplicative complex. (PMID:23093411)
• And-1 together with HJURP regulates the assembly of new CENP-A onto centromeres. (PMID:23184928)
• The Ctf4-CMG complex contains a homodimeric Ctf4 that acts as a platform linking polymerase alpha to the monomeric hCMG complex. (PMID:24255107)
• RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells. (PMID:25602958)
• And-1 coordinates with Claspin for efficient Chk1 activation in response to replication stress. (PMID:26082189)
• Results provide additional evidence suggesting that WDHD1 is involved in the mismatch repair pathway. (PMID:27037360)
• The WDHD1 gene, one of the genes that is upregulated in human papillomavirus E7-expressing cells, was found to play an important role in E7-induced G1 checkpoint abrogation and rereplication (PMID:27099318)
• And-1 interacts with CtIP and that these interactions are required for DNA damage checkpoint maintenance, thereby linking DNA processing with prolonged cell cycle arrest to allow sufficient time for DNA repair. (PMID:27940552)
• important role of And-1 in homologous recombination repair by regulating CtIP-mediated DNA double-strand break end resection (PMID:27940557)
• findings provide important insights into the mechanistic details of human AND-1 function, advancing our understanding of replisome formation during eukaryotic replication. (PMID:28381552)
• AND-1 depletion is incompatible with proliferation, owing to cells accumulating in G2 with activated DNA damage checkpoint (PMID:30082684)
• The study indicated that miR-494 overexpression suppresses epithelial-mesenchymal transition, tumor formation and lymph node metastasis while promoting cholangiocarcinoma (CCA) cell apoptosis through inhibiting WDHD1 in CCA. (PMID:30314946)
• WDHD1 facilitates G1 checkpoint abrogation in HPV E7 expressing cells by modulating GCN5. (PMID:32883234)
• WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer. (PMID:33221821)
• The clinical significance of transcription factor WD repeat and HMG-box DNA binding protein 1 in laryngeal squamous cell carcinoma and its potential molecular mechanism. (PMID:34999279)
• Targeted inhibition of acidic nucleoplasmic DNA-binding protein 1 enhances radiosensitivity of non-small cell lung cancer. (PMID:35065237)
• ZBTB16 inhibits DNA replication and induces cell cycle arrest by targeting WDHD1 transcription in lung adenocarcinoma. (PMID:38654107)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdhd1	ENSDARG00000015998
mus_musculus	Wdhd1	ENSMUSG00000037572
rattus_norvegicus	Wdhd1	ENSRNOG00000011167
drosophila_melanogaster	Ctf4	FBGN0033890
caenorhabditis_elegans		WBGENE00008921

Protein

Protein identifiers

WD repeat and HMG-box DNA-binding protein 1 — O75717 (reviewed: O75717)

Alternative names: Acidic nucleoplasmic DNA-binding protein 1

All UniProt accessions (3): C9JYB3, O75717, H3BSQ1

UniProt curated annotations — full annotation on UniProt →

Function. Core replisome component that acts as a replication initiation factor. Binds directly to the CMG complex and functions as a hub to recruit additional proteins to the replication fork.

Subunit / interactions. Trimer. Interacts with the polymerase alpha catalytic subunit POLA1. Interacts with MCM10. Interacts with DNA2. Interacts with CDC45 and GINS2 subunit of GINS complex; these interactions associate WDHD1 with the CMG helicase complex.

Subcellular location. Nucleus. Nucleoplasm.

Isoforms (2)

UniProt ID	Names	Canonical?
O75717-1	1	yes
O75717-2	2

RefSeq proteins (2): NP_001008397, NP_009017* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR009071	HMG_box_dom	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR022100	WDHD1/CFT4_beta-prop_2nd	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR048591	WDHD1/CFT4_hel	Domain
IPR055339	HMG-box_WDHD1	Domain
IPR057646	WD40_WDHD1_1st	Domain

Pfam: PF12341, PF20946, PF24815, PF24817

UniProt features (122 total): strand 57, modified residue 15, helix 14, turn 8, repeat 7, compositionally biased region 7, region of interest 3, cross-link 3, sequence variant 3, sequence conflict 2, chain 1, splice variant 1, DNA-binding region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5GVA	X-RAY DIFFRACTION	1.85
5OGS	X-RAY DIFFRACTION	2.5
5GVB	X-RAY DIFFRACTION	2.75
7PLO	ELECTRON MICROSCOPY	2.8
7PFO	ELECTRON MICROSCOPY	3.2
8B9D	ELECTRON MICROSCOPY	3.4
6XTY	ELECTRON MICROSCOPY	6.77
2D7L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75717-F1	74.71	0.55

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 (18): 333, 374, 383, 387, 671, 824, 826, 868, 917, 919, 932, 962, 984, 1041, 1090, 397, 1127, 1127

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 236 (showing top): WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, FISCHER_G1_S_CELL_CYCLE, PUJANA_CHEK2_PCC_NETWORK, CREB_Q4, GOCC_NUCLEAR_REPLICATION_FORK, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, GOBP_DNA_DAMAGE_RESPONSE, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GOBP_MITOTIC_CELL_CYCLE, BENPORATH_ES_CORE_NINE_CORRELATED, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS

GO Biological Process (3): mitotic cell cycle (GO:0000278), DNA-templated DNA replication (GO:0006261), DNA repair (GO:0006281)

GO Molecular Function (4): DNA binding (GO:0003677), chromatin binding (GO:0003682), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear replication fork (GO:0043596), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
cellular anatomical structure	2
cell cycle	1
mitotic nuclear division	1
DNA replication	1
DNA metabolic process	1
DNA damage response	1
nucleic acid binding	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear chromosome	1
nucleus	1
replication fork	1
CMG complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDHD1	MCM10	Q7L590	995
WDHD1	TIPIN	Q9BVW5	993
WDHD1	CLSPN	Q9HAW4	991
WDHD1	TIMELESS	Q9UNS1	978
WDHD1	MRC1	P22897	976
WDHD1	CDC45	O75419	970
WDHD1	DNA2	P51530	885
WDHD1	DDX11	Q96FC9	872
WDHD1	CHTF18	Q8WVB6	846
WDHD1	CHTF8	P0CG13	838
WDHD1	GINS4	Q9BRT9	816
WDHD1	SMC3	Q9UQE7	792
WDHD1	DSCC1	Q9BVC3	773
WDHD1	FEN1	P39748	765
WDHD1	DIAPH2	O60879	762

IntAct

88 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
IMP3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.670
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
KAT2A	WDHD1	psi-mi:“MI:0915”(physical association)	0.620
WDHD1	KAT2A	psi-mi:“MI:0915”(physical association)	0.620
WDHD1	KAT2A	psi-mi:“MI:0407”(direct interaction)	0.620
WDHD1	KAT2A	psi-mi:“MI:0403”(colocalization)	0.620
SPIN2B	WDHD1	psi-mi:“MI:0914”(association)	0.530
MGME1	WDHD1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
GREM2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
CPNE5	RAD21	psi-mi:“MI:0914”(association)	0.530
DNA2	WDHD1	psi-mi:“MI:0915”(physical association)	0.400
NETO2	TIA1	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
FOXS1	DDX39A	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
NS1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (215): WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), GINS3 (Co-fractionation), SF3A3 (Co-fractionation), WDHD1 (Co-fractionation), WDHD1 (Co-fractionation), WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), WDHD1 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IC37, A1A4K3, A2CEI4, B1WC10, E9PY46, F1QEB7, F4IDS7, O08658, O13046, O75694, O75717, O95876, P33194, P37199, P59328, Q08D69, Q10569, Q10570, Q16531, Q32NR9, Q3U1J4, Q4ADV7, Q566H4, Q5DQR4, Q5R649, Q5U1Z0, Q5ZLG9, Q6P6Z0, Q6PGF3, Q6PJI9, Q7XWP1, Q802U2, Q805F9, Q8BMG7, Q8C0M0, Q8C456, Q8CEC0, Q8CJF7, Q8K1X1, Q8NFP9

Diamond homologs: A1CUD6, A2AH22, A7TLU2, A8IZG4, A8X8C6, B0R0D7, B0XAF3, B4GDM7, B4JW81, B4LJT7, E7FAG6, F1LTR1, G0SA60, G0SC29, O13046, O13923, O22468, O75717, O76071, O93377, O94527, P0CS38, P0CS39, P0DPA1, P25382, P25569, P26309, P57737, Q06440, Q08E38, Q09028, Q16576, Q1DZQ0, Q24572, Q28D01, Q28DW0, Q292E8, Q3MHL3, Q3SWX8, Q4KLI9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATR	“up-regulates activity”	WDHD1	phosphorylation
WDHD1	“up-regulates activity”	CLSPN	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA 3’-end processing	6	17.6×	8e-05
Transport of Mature mRNA derived from an Intron-Containing Transcript	7	15.9×	5e-05
Transcription of the HIV genome	5	12.9×	2e-03
HIV Life Cycle	5	12.0×	2e-03
mRNA Splicing	7	11.5×	1e-04
mRNA Polyadenylation	8	10.5×	8e-05
RNA Polymerase II Pre-transcription Events	5	10.3×	4e-03
Processing of Capped Intron-Containing Pre-mRNA	8	9.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA transport	5	14.3×	3e-03
negative regulation of translation	6	12.8×	1e-03
RNA splicing	10	9.6×	5e-05
protein import into nucleus	6	9.4×	4e-03
mRNA processing	9	7.7×	7e-04
mRNA splicing, via spliceosome	7	7.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	142
Likely benign	10
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

3810 predictions. Top by Δscore:

Variant	Effect	Δscore
14:54941690:CCTT:C	acceptor_gain	1.0000
14:54941693:T:C	acceptor_gain	1.0000
14:54941693:T:TC	acceptor_gain	1.0000
14:54941695:G:C	acceptor_gain	1.0000
14:54941700:A:AC	acceptor_gain	1.0000
14:54941700:A:C	acceptor_gain	1.0000
14:54941704:C:CT	acceptor_gain	1.0000
14:54941705:A:T	acceptor_gain	1.0000
14:54941709:G:GC	acceptor_gain	1.0000
14:54941726:T:C	acceptor_gain	1.0000
14:54941726:T:TC	acceptor_gain	1.0000
14:54955556:CTGA:C	donor_loss	1.0000
14:54955557:TGACC:T	donor_loss	1.0000
14:54955558:GAC:G	donor_loss	1.0000
14:54955559:ACC:A	donor_loss	1.0000
14:54955560:C:A	donor_loss	1.0000
14:54955692:TGC:T	acceptor_gain	1.0000
14:54955692:TGCC:T	acceptor_loss	1.0000
14:54955694:CCT:C	acceptor_loss	1.0000
14:54955695:C:CA	acceptor_loss	1.0000
14:54955695:C:CC	acceptor_gain	1.0000
14:54962732:TCTCA:T	donor_loss	1.0000
14:54962733:CTCAC:C	donor_loss	1.0000
14:54962734:TCA:T	donor_loss	1.0000
14:54962735:CACC:C	donor_loss	1.0000
14:54962736:A:AC	donor_gain	1.0000
14:54962736:ACCAG:A	donor_loss	1.0000
14:54962737:C:CA	donor_loss	1.0000
14:54962737:C:CC	donor_gain	1.0000
14:54962737:CCAGG:C	donor_gain	1.0000

AlphaMissense

7491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:54944448:A:G	W1025R	0.998
14:54944448:A:T	W1025R	0.998
14:54963084:G:T	A800D	0.998
14:54989196:C:T	G453E	0.998
14:54989209:A:G	W449R	0.998
14:54989209:A:T	W449R	0.998
14:54963048:A:G	L812P	0.997
14:54963096:G:T	A796D	0.997
14:54987341:A:G	W525R	0.997
14:54987341:A:T	W525R	0.997
14:54989197:C:G	G453R	0.997
14:54989197:C:T	G453R	0.997
14:55007300:A:G	W194R	0.997
14:55007300:A:T	W194R	0.997
14:55008355:A:C	S155R	0.997
14:55008355:A:T	S155R	0.997
14:55008357:T:G	S155R	0.997
14:54963088:A:C	Y799D	0.996
14:54963132:A:G	L784P	0.996
14:55000604:A:G	W281R	0.996
14:55000604:A:T	W281R	0.996
14:55010375:C:G	R92P	0.996
14:55013579:C:T	G32E	0.996
14:54963085:C:G	A800P	0.995
14:54967382:A:C	C692W	0.995
14:54981577:A:G	W676R	0.995
14:54981577:A:T	W676R	0.995
14:54989144:G:C	F470L	0.995
14:54989144:G:T	F470L	0.995
14:54989146:A:G	F470L	0.995

dbSNP variants (sampled 300 via entrez): RS1000021160 (14:55011673 ATTTATT>A), RS1000034619 (14:54974475 C>A,T), RS1000052505 (14:55022240 G>A,C), RS1000069239 (14:55016078 G>A), RS1000072326 (14:55026825 C>T), RS1000091189 (14:55022143 G>C,T), RS1000093661 (14:54980376 G>A,C), RS1000117708 (14:55023548 C>T), RS1000144229 (14:55026512 G>C,T), RS1000211846 (14:54986415 G>A), RS1000219645 (14:54947792 A>T), RS1000321054 (14:55028433 T>A), RS1000322278 (14:54992421 C>T), RS1000384183 (14:55021213 G>T), RS1000433831 (14:54992763 A>C)

Disease associations

OMIM: gene MIM:608126 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002365_6	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 2 peripheral neuropathy)	3.000000e-06
GCST007576_130	Chronotype	7.000000e-09
GCST90002390_263	Mean corpuscular hemoglobin	1.000000e-17
GCST90002392_450	Mean corpuscular volume	3.000000e-18
GCST90002397_74	Mean spheric corpuscular volume	3.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0008328	chronotype measurement
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295681 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	4
bisphenol A	decreases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Cyclosporine	decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Estradiol	decreases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
tetrahydropalmatine	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118656	Binding	Binding affinity to WDHD1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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