HOXC8

Summary

HOXC8 (homeobox C8, HGNC:5129) is a protein-coding gene on chromosome 12q13.13, encoding Homeobox protein Hox-C8 (P31273). Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXC genes located in a cluster on chromosome 12. The product of this gene may play a role in the regulation of cartilage differentiation. It could also be involved in chondrodysplasias or other cartilage disorders.

Source: NCBI Gene 3224 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 30 total
• Transcription factor: yes — 16 downstream targets (CollecTRI)
• MANE Select transcript: NM_022658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5129
Approved symbol	HOXC8
Name	homeobox C8
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000037965
Ensembl biotype	protein_coding
OMIM	142970
Entrez	3224

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000040584

RefSeq mRNA: 1 — MANE Select: NM_022658 NM_022658

CCDS: CCDS8870

Canonical transcript exons

ENST00000040584 — 2 exons

Exon	Start	End
ENSE00000748009	54008985	54009720
ENSE00000838338	54011089	54012769

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 85.30.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8436 / max 110.7990, expressed in 444 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125854	1.8436	444

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	85.30	gold quality
gastrocnemius	UBERON:0001388	83.80	gold quality
muscle of leg	UBERON:0001383	82.39	gold quality
gluteal muscle	UBERON:0002000	81.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.98	gold quality
triceps brachii	UBERON:0001509	80.21	gold quality
muscle organ	UBERON:0001630	79.77	gold quality
diaphragm	UBERON:0001103	78.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.53	gold quality
left uterine tube	UBERON:0001303	76.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.41	gold quality
tibial nerve	UBERON:0001323	74.04	gold quality
metanephros cortex	UBERON:0010533	73.78	gold quality
vastus lateralis	UBERON:0001379	73.45	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.26	gold quality
popliteal artery	UBERON:0002250	73.10	gold quality
tibial artery	UBERON:0007610	73.09	gold quality
quadriceps femoris	UBERON:0001377	72.80	gold quality
skeletal muscle tissue	UBERON:0001134	72.55	gold quality
tongue squamous epithelium	UBERON:0006919	72.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.87	gold quality
left adrenal gland cortex	UBERON:0035825	71.71	gold quality
right ovary	UBERON:0002118	71.19	gold quality
left adrenal gland	UBERON:0001234	71.09	gold quality
adrenal cortex	UBERON:0001235	70.71	gold quality
right adrenal gland cortex	UBERON:0035827	69.63	gold quality
right adrenal gland	UBERON:0001233	69.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.25	gold quality
adrenal gland	UBERON:0002369	69.22	gold quality
left ovary	UBERON:0002119	69.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

16 targets.

Target	Regulation
AR	Repression
BMP2
DST	Unknown
HOXC8
HOXD4
LLGL1
NCAM1	Unknown
NKD2	Repression
PCNA	Activation
SLC11A1
SMAD1
SMAD6	Repression
SPP1
TNFRSF11B	Unknown
TSC1
TTF1

JASPAR motifs

Motif	Name	Family
MA1505.1	HOXC8	HOX
MA1505.2	HOXC8	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): AR, BPTF, HOXC8, HOXC9, KDM6A, KMT2A, NCOA3

miRNA regulators (miRDB)

136 targeting HOXC8, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
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-6825-5P	99.96	69.81	3431
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-338-5P	99.92	72.34	2951

Literature-anchored findings (GeneRIF, showing 25)

• overexpression associated with loss of tumor differentiation in human prostate cancer; may play role in acquisition of invasive/metastatic phenotype (PMID:11813208)
• Androgen-independent cell line DU145 cells lack PLZF gene expression, resulting in the upregulation of Pbx1 and HoxC8 expression. The Pbx1-HoxC8 heterocomplex may lead to androgen-independent growth in prostate cancer. (PMID:16637071)
• Ratio of microRNA to HOXC8 mRNA may be an indicator of the metastatic capability of breast tumors. (PMID:20736365)
• a complex role for HOXC8 in prostate cancer, promoting invasiveness while inhibiting AR-mediated gene induction at androgen response element-regulated genes associated with differentiated function of the prostate (PMID:21047772)
• HOXC8 expression is inversely related to pancreatic ductal adenocarcinoma progression and metastasis. (PMID:21712827)
• HOXC8 can be used as a prognostic marker in esophageal squamous cell carcinoma (PMID:24525058)
• HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression. (PMID:24810778)
• miR-196a was over-expressed in cervical cancer cells, while an absence of HOXC8 expression was observed. (PMID:24817935)
• Ectopic expression of HoxC8 inhibits nasopharyngeal carcinoma cell growth in vitro and in vivo, modulates glycolysis and regulates the expression of tricarboxylic acid (TCA) cycle-related genes. (PMID:25745994)
• embigin is regulated by HOXC8 and its loss plays an important role in the progression of breast tumors (PMID:26090721)
• Upregulated HOXC8 expression was associated with oxaliplatin resistance in hepatocellular carcinoma. (PMID:26123838)
• Owing to the overexpression of Homeobox C8 (HOXC8), findings implied that HOXC8 is involved in the progression of epithelial ovarian cancer (EOC) and could be a potential therapeutical approach of EOC. (PMID:26763553)
• HOXC8 knockdown led to inhibition of tumor cell proliferation and migration in vitro by inhibiting MMP-9 expression and tumor growth in vivo. The results strongly suggest that HOXC8 is involved in the tumorigenesis of osteosarcoma and might serve as a novel predictor for patients’ outcome. (PMID:27651160)
• High expression of HOXC8 is associated with laryngeal squamous cell carcinoma. (PMID:27658780)
• Results show that HOXC8 is consistently downregulated in stem/progenitor cells of all breast molecular subtypes, thus representing a putative tumor suppressor candidate. Also, downregulated expression of HOXC8 is associated with DNA methylation at the gene promoter and expression of miR196 family members. Taken together, study establishes HOXC8 as a suppressor of stemness and transformation in the mammary gland lineage. (PMID:28202042)
• these data indicate that E-cadherin is a target gene of HOXC8 and that the loss of E-cadherin promotes the growth and migration of NSCLC. (PMID:31202850)
• our results showed that the HOXC8-MGP axis played an important role in the tumorigenesis of Triple-negative breast cancer (TNBC) and might be a promising therapeutic target for TNBC treatment (PMID:31264274)
• Homeobox C8 inhibited the osteo-/dentinogenic differentiation and migration ability of stem cells of the apical papilla via activating KDM1A. (PMID:32246725)
• MiR-148a-3p may contribute to flawed decidualization in recurrent implantation failure by modulating HOXC8. (PMID:32772270)
• An Integrated Genomic Approach Identifies HOXC8 as an Upstream Regulator in Ovarian Endometrioma. (PMID:32877504)
• HOXC6/8/10/13 predict poor prognosis and associate with immune infiltrations in glioblastoma. (PMID:34763232)
• HOXC8 alleviates high glucose-triggered damage of trophoblast cells during gestational diabetes mellitus via activating TGFbeta1-mediated Notch1 pathway. (PMID:36308681)
• Human papillomavirus type 16 E7 promotes cell viability and migration in cervical cancer by regulating the miR-23a/HOXC8 axis. (PMID:38348790)
• DNA Methylation-Regulated HOXC8’s Role in HER2-Positive Breast Cancer Function and its Contribution to Herceptin Resistance. (PMID:38531796)
• N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1. (PMID:38641828)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxc8a	ENSDARG00000070346
mus_musculus	Hoxc8	ENSMUSG00000001657
rattus_norvegicus	Hoxc8	ENSRNOG00000028619

Paralogs (42): HOXA11 (ENSG00000005073), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA5 (ENSG00000106004), HOXA6 (ENSG00000106006), HOXA13 (ENSG00000106031), TLX1 (ENSG00000107807), HOXB6 (ENSG00000108511), TLX2 (ENSG00000115297), HOXB8 (ENSG00000120068), HOXB5 (ENSG00000120075), HOXB3 (ENSG00000120093), HOXB1 (ENSG00000120094), HOXA7 (ENSG00000122592), HOXC13 (ENSG00000123364), HOXC11 (ENSG00000123388), HOXC12 (ENSG00000123407), HOXD1 (ENSG00000128645), HOXD3 (ENSG00000128652), HOXD9 (ENSG00000128709), HOXD10 (ENSG00000128710), HOXD11 (ENSG00000128713), HOXD13 (ENSG00000128714), PDX1 (ENSG00000139515), HOXB13 (ENSG00000159184), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXC10 (ENSG00000180818), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-C8 — P31273 (reviewed: P31273)

Alternative names: Homeobox protein Hox-3A

All UniProt accessions (1): P31273

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Subunit / interactions. Interacts with HOMEZ. Forms a DNA-binding heterodimer with transcription factor PBX1.

Subcellular location. Nucleus.

Similarity. Belongs to the Antp homeobox family.

RefSeq proteins (1): NP_073149* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR001827	Homeobox_Antennapedia_CS	Conserved_site
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050948	Antp_homeobox_TF	Family

Pfam: PF00046

UniProt features (9 total): compositionally biased region 3, region of interest 2, chain 1, DNA-binding region 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31273-F1	65.68	0.25

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9762293	Regulation of CDH11 gene transcription

MSigDB gene sets: 153 (showing top): ACTACCT_MIR196A_MIR196B, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_NEUROGENESIS, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GCGCTTT_MIR518B_MIR518C_MIR518D, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, FREAC3_01, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, AAAGGGA_MIR204_MIR211, AACTTT_UNKNOWN, GFI1_01

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), anterior/posterior pattern specification (GO:0009952), neuron differentiation (GO:0030182), skeletal system morphogenesis (GO:0048705), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), microtubule cytoskeleton (GO:0015630)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of CDH11 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
regionalization	1
cell differentiation	1
generation of neurons	1
skeletal system development	1
animal organ morphogenesis	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoskeleton	1

Protein interactions and networks

STRING

1124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXC8	TAPT1	Q6NXT6	811
HOXC8	HOMEZ	Q8IX15	716
HOXC8	BPTF	Q12830	608
HOXC8	SMAD6	O43541	591
HOXC8	ISL1	P20663	571
HOXC8	ZHX1	Q9UKY1	568
HOXC8	SMAD2	Q15796	565
HOXC8	WDR5	P61964	548
HOXC8	TMEM26	Q6ZUK4	520
HOXC8	SMARCA1	P28370	501
HOXC8	FOXO1	Q12778	484
HOXC8	SMAD1	Q15797	471
HOXC8	SMAD7	O15105	467
HOXC8	DICER1	Q9UPY3	459
HOXC8	PRDM16	Q9HAZ2	452

IntAct

315 interactions, top by confidence:

A	B	Type	Score
HOXC8	SNX17	psi-mi:“MI:0915”(physical association)	0.670
HOXC8	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	TRIB3	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PBX4	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PBX2	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	ANKS1A	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	DZIP3	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	CEP70	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	TLE5	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
GYS1	HOXC8	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	TBC1D1	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	CCM2	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PDE4DIP	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	LDLRAP1	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	BLZF1	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	POU6F2	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	LHX3	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	HOXC8	psi-mi:“MI:0915”(physical association)	0.560
PAX6	HOXC8	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	TNS2	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	HOXC8	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	KRT35	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PAX5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (128): HOXC8 (Affinity Capture-MS), RBPMS (Two-hybrid), HOXC8 (Two-hybrid), HOXC8 (Two-hybrid), HOXC8 (Two-hybrid), HOXC8 (Two-hybrid), TRAF1 (Two-hybrid), PRDM6 (Two-hybrid), ANKS1A (Two-hybrid), GSTO2 (Two-hybrid), TBC1D1 (Two-hybrid), PLA2G10 (Two-hybrid), TRIP6 (Two-hybrid), NID2 (Two-hybrid), ZMAT5 (Two-hybrid)

ESM2 similar proteins: A0A1W2PPK0, A0A1W2PPM1, A1YFT7, A2D5V0, A2T7D1, A7Y7W3, A9L937, B0VXK3, F1Q4R9, G3X9P6, G3X9U1, O43364, P09025, P09092, P09632, P17278, P17481, P24342, P28358, P28359, P31245, P31246, P31263, P31273, Q0VCS4, Q1ECY2, Q1KKS8, Q1KKT2, Q1KKV1, Q1KKV4, Q1KKZ4, Q1KKZ6, Q3LTE0, Q3UT54, Q4JM65, Q4KL20, Q5TM83, Q5TM84, Q68EH7, Q6JIY4

Diamond homologs: A1YFA5, A1YFD8, A1YGK7, A2D5K9, A2D5Y4, A2T7F3, B0W1V2, O42504, P02830, P02832, P02833, P04476, P09013, P09014, P09016, P09017, P09019, P09020, P09021, P09023, P09024, P09025, P09067, P09071, P09074, P09077, P09079, P09080, P09092, P09629, P09630, P09632, P09634, P09636, P09637, P10284, P10629, P14838, P14839, P14840

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
KDM6A	“up-regulates quantity by expression”	HOXC8	“transcriptional regulation”
SMAD6	“up-regulates activity”	HOXC8	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 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
Keratinization	17	15.3×	2e-13
FCGR3A-mediated phagocytosis	5	15.1×	3e-03
Signaling by ROBO receptors	5	10.0×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	20.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

255 predictions. Top by Δscore:

Variant	Effect	Δscore
12:54011364:G:GT	donor_gain	1.0000
12:54011375:GGAC:G	donor_gain	1.0000
12:54011376:GAC:G	donor_gain	1.0000
12:54009717:CACGG:C	donor_loss	0.9900
12:54009718:ACGGT:A	donor_loss	0.9900
12:54009719:CGGT:C	donor_loss	0.9900
12:54009721:G:GA	donor_loss	0.9900
12:54009721:G:GG	donor_gain	0.9900
12:54009722:T:A	donor_loss	0.9900
12:54011087:A:AG	acceptor_gain	0.9900
12:54011088:G:GG	acceptor_gain	0.9900
12:54011088:GCTCC:G	acceptor_gain	0.9900
12:54011337:G:GT	donor_gain	0.9900
12:54011365:A:T	donor_gain	0.9900
12:54011378:C:CG	donor_gain	0.9900
12:54011378:C:G	donor_gain	0.9900
12:54009719:CG:C	donor_gain	0.9800
12:54009720:GG:G	donor_gain	0.9800
12:54011085:CCA:C	acceptor_loss	0.9800
12:54011086:CAGC:C	acceptor_loss	0.9800
12:54011087:A:AT	acceptor_loss	0.9800
12:54011088:GCT:G	acceptor_gain	0.9800
12:54011178:C:G	acceptor_gain	0.9800
12:54011355:G:GT	donor_gain	0.9800
12:54011364:G:T	donor_gain	0.9800
12:54011391:A:T	donor_gain	0.9800
12:54011082:T:TA	acceptor_gain	0.9700
12:54011088:GCTC:G	acceptor_gain	0.9700
12:54011173:T:TA	acceptor_gain	0.9700
12:54009718:ACGG:A	donor_loss	0.9600

AlphaMissense

1597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:54009705:T:A	W141R	1.000
12:54009705:T:C	W141R	1.000
12:54009707:G:C	W141C	1.000
12:54009707:G:T	W141C	1.000
12:54009709:T:C	M142T	1.000
12:54011118:T:A	Y156N	1.000
12:54011118:T:C	Y156H	1.000
12:54011118:T:G	Y156D	1.000
12:54011119:A:G	Y156C	1.000
12:54011132:G:C	Q160H	1.000
12:54011132:G:T	Q160H	1.000
12:54011143:T:A	L164Q	1.000
12:54011143:T:C	L164P	1.000
12:54011143:T:G	L164R	1.000
12:54011145:G:A	E165K	1.000
12:54011146:A:C	E165A	1.000
12:54011146:A:T	E165V	1.000
12:54011147:A:C	E165D	1.000
12:54011147:A:T	E165D	1.000
12:54011150:G:C	K166N	1.000
12:54011150:G:T	K166N	1.000
12:54011151:G:A	E167K	1.000
12:54011153:G:C	E167D	1.000
12:54011153:G:T	E167D	1.000
12:54011154:T:A	F168I	1.000
12:54011154:T:C	F168L	1.000
12:54011154:T:G	F168V	1.000
12:54011155:T:C	F168S	1.000
12:54011155:T:G	F168C	1.000
12:54011156:T:A	F168L	1.000

dbSNP variants (sampled 300 via entrez): RS1000190438 (12:54009210 G>A,C), RS1001415308 (12:54012543 C>T), RS1001904470 (12:54010305 A>C), RS1002318335 (12:54010732 C>T), RS1002568484 (12:54013187 C>A), RS1002751459 (12:54007003 G>A,T), RS1003419937 (12:54009634 C>T), RS1003523096 (12:54012013 C>A,T), RS1003577088 (12:54011648 A>G), RS1004195294 (12:54011605 G>A), RS1004536224 (12:54008962 C>T), RS1004673728 (12:54009209 AG>A), RS1004879610 (12:54011898 A>T), RS1005675157 (12:54007685 C>G,T), RS1006275914 (12:54013130 G>C)

Disease associations

OMIM: gene MIM:142970 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_70	Waist-to-hip ratio adjusted for BMI	4.000000e-13
GCST005957_6	Waist-to-hip ratio adjusted for BMI (age <50)	6.000000e-06
GCST005958_9	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-08
GCST005962_20	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

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
(+)-JQ1 compound	decreases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
bisphenol A	decreases expression	1
lead acetate	increases expression	1
arsenite	increases methylation	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	decreases expression, increases activity	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Cytarabine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	affects expression	1
Thapsigargin	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2Z9	SEES3-1V human HOXC8, clone1	Embryonic stem cell	Male
CVCL_A3A0	SEES3-1V human HOXC8, clone2	Embryonic stem cell	Male
CVCL_A3A1	SEES3-1V human HOXC8, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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