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HOXC12

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Summary

HOXC12 (homeobox C12, HGNC:5124) is a protein-coding gene on chromosome 12q13.13, encoding Homeobox protein Hox-C12 (P31275). 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.

Source: NCBI Gene 3228 — RefSeq curated summary.

At a glance

  • GWAS associations: 27
  • Clinical variants (ClinVar): 48 total
  • MANE Select transcript: NM_173860

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:5124
Approved symbolHOXC12
Namehomeobox C12
Location12q13.13
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000123407
Ensembl biotypeprotein_coding
OMIM142975
Entrez3228

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000243103

RefSeq mRNA: 1 — MANE Select: NM_173860 NM_173860

CCDS: CCDS8866

Canonical transcript exons

ENST00000243103 — 2 exons

ExonStartEnd
ENSE000008383295395632853958956
ENSE000010592665395490353955539

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 81.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4082 / max 176.7636, expressed in 46 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1258140.304840
1258150.103415

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047381.05silver quality
skin of legUBERON:000151167.27gold quality
sural nerveUBERON:001548865.68silver quality
popliteal arteryUBERON:000225063.54gold quality
tibial arteryUBERON:000761063.50gold quality
zone of skinUBERON:000001461.26gold quality
skin of abdomenUBERON:000141659.63gold quality
subcutaneous adipose tissueUBERON:000219055.87gold quality
biceps brachiiUBERON:000150752.35gold quality
skin of hipUBERON:000155450.92silver quality
Brodmann (1909) area 46UBERON:000648350.76gold quality
deltoidUBERON:000147647.02gold quality
substantia nigra pars compactaUBERON:000196546.68gold quality
aortaUBERON:000094745.56gold quality
lateral globus pallidusUBERON:000247645.29gold quality
lateral nuclear group of thalamusUBERON:000273644.64gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451143.37gold quality
amniotic fluidUBERON:000017343.17gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450242.91gold quality
olfactory segment of nasal mucosaUBERON:000538642.84gold quality
Brodmann (1909) area 23UBERON:001355442.82gold quality
skeletal muscle tissueUBERON:000113442.70gold quality
secondary oocyteCL:000065542.57gold quality
epithelium of nasopharynxUBERON:000195142.11gold quality
myocardiumUBERON:000234942.00gold quality
adipose tissueUBERON:000101341.88gold quality
nasal cavity mucosaUBERON:000182641.70gold quality
globus pallidusUBERON:000187541.68gold quality
vastus lateralisUBERON:000137941.41gold quality
quadriceps femorisUBERON:000137741.37gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no2.13

Regulation

Is transcription factor: yes

JASPAR motifs

MotifNameFamily
MA0906.1HOXC12HOX
MA0906.2HOXC12HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): EZH2

Literature-anchored findings (GeneRIF, showing 1)

  • The microdeletions share a minimal non-coding region overlap upstream of HOXC13, with variable phenotypes depending upon HOXC13, HOXC12 or the HOTAIR lncRNA inclusion. Identification of 5’ HOXC microdeletions highlights the importance of transcriptional regulators in the aetiology of severe lower limb malformations and will improve their diagnosis and management (PMID:26729820)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriohoxc12aENSDARG00000070352
danio_reriohoxc12bENSDARG00000103133
mus_musculusHoxc12ENSMUSG00000050328
rattus_norvegicusHoxc12ENSRNOG00000016116

Paralogs (42): HOXA11 (ENSG00000005073), HOXC8 (ENSG00000037965), 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), 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-C12 — P31275 (reviewed: P31275)

Alternative names: Homeobox protein Hox-3F

All UniProt accessions (1): P31275

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.

Subcellular location. Nucleus.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_776272* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001356HDDomain
IPR009057Homeodomain-like_sfHomologous_superfamily
IPR017970Homeobox_CSConserved_site
IPR020479HD_metazoaDomain

Pfam: PF00046

UniProt features (5 total): region of interest 2, chain 1, DNA-binding region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P31275-F163.340.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, AP4_Q6, TAL1ALPHAE47_01, CHX10_01, USF_C, CAGCTG_AP4_Q5, FREAC3_01, TGACATY_UNKNOWN, GATA1_04, AACTTT_UNKNOWN, FOXJ2_02, YNGTTNNNATT_UNKNOWN, AR_01, TAATTA_CHX10_01

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (3): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
DNA-templated transcription1
regulation of gene expression1
regulation of RNA biosynthetic process1
regulation of DNA-templated transcription1
transcription by RNA polymerase II1
chromatin1
RNA polymerase II transcription regulatory region sequence-specific DNA binding1
DNA-binding transcription factor activity1
regulation of transcription by RNA polymerase II1
double-stranded DNA binding1
sequence-specific DNA binding1
nucleic acid binding1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HOXC12HOXC5Q00444567
HOXC12ISL1P20663524
HOXC12KRT35Q92764441
HOXC12KRT32Q14532418
HOXC12KDM1AO60341391
HOXC12KCNQ1P51787387
HOXC12HOXC6P09630381
HOXC12HOXC11O43248375
HOXC12IGF2RP11717374
HOXC12HOXC4P09017372
HOXC12PPP1R36Q96LQ0357
HOXC12SLIRPQ9GZT3353
HOXC12STAU1O95793350
HOXC12HOXA13P31271344
HOXC12RCOR1Q9UKL0329

IntAct

3 interactions, top by confidence:

ABTypeScore
HOXC12psi-mi:“MI:0915”(physical association)0.370
HOXC12SORL1psi-mi:“MI:0914”(association)0.350

BioGRID (5): XPNPEP1 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), SUPT16H (Affinity Capture-MS), KLHL21 (Affinity Capture-MS)

ESM2 similar proteins: A1YER7, A1YF08, A1YFD8, A1YFY3, A1YG01, A1YG85, A2D4P8, A2D4R4, A2D5I1, A2D649, A2T6H5, A2T6X6, A2T6Z0, A2T748, A2T756, A2T7H5, A2T7J2, P06798, P09016, P09017, P09023, P09024, P10284, P10628, P13378, P14653, P17277, P17483, P17509, P18111, P18864, P23463, P23813, P31259, P31275, P31276, P31277, P31310, P47902, P50207

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, G5EFY5, O14627, O42502, O42506, O43248, P02835, P09013, P09067, P09079, P09087, P09631, P09633, P10038, P10179, P17482, P17919, P20615, P23812, P24061, P24341, P24342, P24343, P24344, P28358, P28359, P31257, P31260, P31263, P31268, P31269, P31271, P31272, P31274, P31275

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance43
Likely benign3
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

178 predictions. Top by Δscore:

VariantEffectΔscore
12:53955537:GCG:Gdonor_gain1.0000
12:53956490:TC:Tdonor_gain1.0000
12:53955540:G:GGdonor_gain0.9900
12:53955541:TAA:Tdonor_loss0.9900
12:53956323:CCCA:Cacceptor_loss0.9900
12:53956325:CAG:Cacceptor_loss0.9900
12:53956326:A:AGacceptor_gain0.9900
12:53956327:G:GAacceptor_loss0.9900
12:53956327:G:GGacceptor_gain0.9900
12:53956327:GGC:Gacceptor_gain0.9900
12:53956327:GGCGC:Gacceptor_gain0.9900
12:53955605:GAC:Gdonor_gain0.9800
12:53955496:C:Gdonor_gain0.9700
12:53955984:G:GTdonor_gain0.9700
12:53956003:G:Tdonor_gain0.9700
12:53956322:A:AGacceptor_gain0.9700
12:53956323:C:Gacceptor_gain0.9700
12:53956326:AG:Aacceptor_gain0.9700
12:53956326:AGGC:Aacceptor_gain0.9700
12:53956327:GG:Gacceptor_gain0.9700
12:53956327:GGCG:Gacceptor_gain0.9700
12:53955502:ATCGC:Adonor_gain0.9600
12:53955612:C:Gdonor_gain0.9600
12:53955973:GGAT:Gdonor_gain0.9600
12:53955974:G:GTdonor_gain0.9600
12:53955503:TCGCC:Tdonor_gain0.9400
12:53955617:G:Tdonor_gain0.9400
12:53955666:G:GTdonor_gain0.9300
12:53955995:G:GTdonor_gain0.9300
12:53955536:AGCG:Adonor_gain0.9200

AlphaMissense

1800 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:53956369:C:AR218S1.000
12:53956378:T:CY221H1.000
12:53956378:T:GY221D1.000
12:53956379:A:GY221C1.000
12:53956394:T:CL226P1.000
12:53956396:G:CA227P1.000
12:53956403:T:AL229Q1.000
12:53956403:T:CL229P1.000
12:53956403:T:GL229R1.000
12:53956406:A:TE230V1.000
12:53956414:T:AF233I1.000
12:53956414:T:CF233L1.000
12:53956414:T:GF233V1.000
12:53956415:T:CF233S1.000
12:53956415:T:GF233C1.000
12:53956416:T:AF233L1.000
12:53956416:T:GF233L1.000
12:53956429:T:AF238I1.000
12:53956429:T:CF238L1.000
12:53956430:T:CF238S1.000
12:53956430:T:GF238C1.000
12:53956431:C:AF238L1.000
12:53956431:C:GF238L1.000
12:53956433:T:AI239N1.000
12:53956433:T:CI239T1.000
12:53956433:T:GI239S1.000
12:53956457:T:CL247P1.000
12:53956459:T:CS248P1.000
12:53956475:T:AL253H1.000
12:53956475:T:CL253P1.000

dbSNP variants (sampled 300 via entrez): RS1000227690 (12:53952924 A>G), RS1000727625 (12:53957040 G>A,T), RS1001086354 (12:53956829 G>C), RS1001750940 (12:53959315 T>C), RS1001772622 (12:53957315 G>A), RS1002345885 (12:53957909 G>A), RS1002566040 (12:53956360 C>A,G,T), RS1002849613 (12:53955293 G>A,C), RS1003793257 (12:53955448 C>T), RS1003909331 (12:53955719 G>A), RS1004757332 (12:53958988 T>A), RS1004806893 (12:53954408 C>G,T), RS1004983699 (12:53953814 A>G), RS1005115148 (12:53959372 A>G), RS1005187268 (12:53955999 T>C)

Disease associations

OMIM: gene MIM:142975 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

StudyTraitp-value
GCST002782_45Waist-to-hip ratio adjusted for body mass index4.000000e-12
GCST002782_46Waist-to-hip ratio adjusted for body mass index3.000000e-13
GCST002782_47Waist-to-hip ratio adjusted for body mass index3.000000e-13
GCST002782_48Waist-to-hip ratio adjusted for body mass index2.000000e-13
GCST004505_43Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)7.000000e-11
GCST004505_44Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)7.000000e-13
GCST004507_17Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)2.000000e-10
GCST004507_34Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)4.000000e-09
GCST004508_3Waist-to-hip ratio adjusted for BMI in non-smokers3.000000e-08
GCST004508_4Waist-to-hip ratio adjusted for BMI in non-smokers9.000000e-11
GCST005956_70Waist-to-hip ratio adjusted for BMI4.000000e-13
GCST005957_6Waist-to-hip ratio adjusted for BMI (age <50)6.000000e-06
GCST005958_9Waist-to-hip ratio adjusted for BMI (age >50)1.000000e-08
GCST005962_20Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)7.000000e-13
GCST012228_549Waist-hip index5.000000e-10
GCST012230_43Waist-to-hip ratio adjusted for BMI2.000000e-10
GCST90020024_272A body shape index5.000000e-24
GCST90020025_79Waist-to-hip ratio adjusted for BMI1.000000e-10
GCST90020025_81Waist-to-hip ratio adjusted for BMI7.000000e-32
GCST90020025_83Waist-to-hip ratio adjusted for BMI7.000000e-38
GCST90020026_493Hip index2.000000e-13
GCST90020026_494Hip index6.000000e-13
GCST90020027_1708Waist-hip index9.000000e-11
GCST90020027_1710Waist-hip index2.000000e-31
GCST90020027_1712Waist-hip index1.000000e-37
GCST90020029_451Waist circumference adjusted for body mass index1.000000e-20
GCST90020029_452Waist circumference adjusted for body mass index2.000000e-15

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0007788BMI-adjusted waist-hip ratio
EFO:0004318smoking behavior
EFO:0008007age at assessment
EFO:0008343sex interaction measurement
EFO:0007789BMI-adjusted waist circumference
EFO:0008039BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Aincreases methylation1
arseniteincreases methylation1
benzo(e)pyreneincreases methylation1
aflatoxin B2decreases methylation1
Arsenicdecreases expression1
Benzo(a)pyreneaffects methylation1
Methapyrileneincreases methylation1
Phthalic Acidsdecreases expression1
Aflatoxin B1increases methylation1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot