ANHX

Summary

ANHX (anomalous homeobox, HGNC:40024) is a protein-coding gene on chromosome 12q24.33, encoding Anomalous homeobox protein (E9PGG2).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of skeletal muscle cell proliferation; regulation of transcription by RNA polymerase II; and skeletal muscle fiber development. Predicted to be part of transcription regulator complex. Predicted to be active in nucleus.

Source: NCBI Gene 647589 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_001372060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40024
Approved symbol	ANHX
Name	anomalous homeobox
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000227059
Ensembl biotype	protein_coding
Entrez	647589

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000419717, ENST00000545940, ENST00000673940

RefSeq mRNA: 2 — MANE Select: NM_001372060 NM_001191054, NM_001372060

CCDS: CCDS53855, CCDS91786

Canonical transcript exons

ENST00000545940 — 10 exons

Exon	Start	End
ENSE00001617662	133226318	133226438
ENSE00001622610	133235807	133235877
ENSE00001648442	133218312	133218971
ENSE00001653494	133231517	133231644
ENSE00001656095	133226936	133227152
ENSE00001674517	133227824	133227947
ENSE00001718184	133219283	133219367
ENSE00001734196	133234108	133234378
ENSE00003896409	133225536	133225828
ENSE00003897678	133221205	133221352

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 85.29.

Top tissues by expression

166 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	85.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.15	gold quality
trabecular bone tissue	UBERON:0002483	84.82	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.53	silver quality
sperm	CL:0000019	84.26	silver quality
endothelial cell	CL:0000115	84.04	silver quality
mammary duct	UBERON:0001765	83.98	silver quality
myocardium	UBERON:0002349	83.75	silver quality
gingival epithelium	UBERON:0001949	83.16	silver quality
vena cava	UBERON:0004087	81.40	silver quality
ventral tegmental area	UBERON:0002691	80.56	silver quality
esophagus squamous epithelium	UBERON:0006920	80.09	gold quality
heart right ventricle	UBERON:0002080	79.81	gold quality
cardia of stomach	UBERON:0001162	79.05	silver quality
inferior vagus X ganglion	UBERON:0005363	79.04	silver quality
dorsal plus ventral thalamus	UBERON:0001897	78.69	silver quality
lower lobe of lung	UBERON:0008949	78.25	silver quality
cerebellar vermis	UBERON:0004720	78.22	silver quality
cartilage tissue	UBERON:0002418	78.21	silver quality
pharyngeal mucosa	UBERON:0000355	78.15	silver quality
body of tongue	UBERON:0011876	78.10	silver quality
tongue	UBERON:0001723	77.90	silver quality
decidua	UBERON:0002450	77.90	silver quality
lateral globus pallidus	UBERON:0002476	77.79	silver quality
deltoid	UBERON:0001476	77.76	silver quality
substantia nigra pars compacta	UBERON:0001965	77.66	silver quality
pericardium	UBERON:0002407	77.64	silver quality
substantia nigra pars reticulata	UBERON:0001966	77.63	silver quality
lateral nuclear group of thalamus	UBERON:0002736	77.57	silver quality
superior vestibular nucleus	UBERON:0007227	77.51	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting ANHX, 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-4481	100.00	66.42	1669
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-599	98.32	66.99	1037
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-592	96.59	67.59	817
HSA-MIR-6767-5P	90.00	62.41	97

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	six4a	ENSDARG00000004695
danio_rerio	six4b	ENSDARG00000031983
danio_rerio	six7	ENSDARG00000070107
drosophila_melanogaster	Optix	FBGN0025360
drosophila_melanogaster	Six4	FBGN0027364
caenorhabditis_elegans		WBGENE00000453
caenorhabditis_elegans		WBGENE00000455
caenorhabditis_elegans		WBGENE00006775

Paralogs (6): SIX4 (ENSG00000100625), SIX1 (ENSG00000126778), SIX3 (ENSG00000138083), SIX2 (ENSG00000170577), SIX5 (ENSG00000177045), SIX6 (ENSG00000184302)

Protein

Protein identifiers

Anomalous homeobox protein — E9PGG2 (reviewed: E9PGG2)

All UniProt accessions (3): E9PGG2, A0A669KBG6, A0A6E1YDD0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

RefSeq proteins (2): NP_001177983, NP_001358989* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR008422	KN_HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR031701	SIX1_SD	Domain

Pfam: PF05920, PF16878

UniProt features (7 total): sequence conflict 3, chain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-E9PGG2-F1	68.30	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 15 (showing top): GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, chr12q24, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, SRC_UP.V1_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR6728_3P, MIR506_5P, MIR599, GSE13485_DAY1_VS_DAY3_YF17D_VACCINE_PBMC_UP, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, PULVER_FOREY_PERTURB_ACCUMULATION_G1_S, PULVER_FOREY_PERTURB_ATTRITION_S, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GSE27291_0H_VS_6H_STIM_GAMMADELTA_TCELL_DN

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), regulation of skeletal muscle cell proliferation (GO:0014857), skeletal muscle fiber development (GO:0048741), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677)

GO Cellular Component (2): nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
skeletal muscle cell proliferation	1
regulation of cell population proliferation	1
skeletal muscle tissue development	1
myotube cell development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANHX	NANOGNB	Q7Z5D8	645
ANHX	LRRC71	Q8N4P6	567
ANHX	ARGFX	A6NJG6	535
ANHX	LEUTX	A8MZ59	531
ANHX	DUXB	A0A1W2PPF3	513
ANHX	TPRX1	Q8N7U7	463
ANHX	LYPD6B	Q8NI32	453
ANHX	DUXA	A6NLW8	433
ANHX	ZNF415	Q09FC8	419
ANHX	CLK4	Q9HAZ1	418
ANHX	DPRX	A6NFQ7	405
ANHX	HOXB1	P14653	384
ANHX	DPPA3	Q6W0C5	383
ANHX	GDF3	Q9NR23	381
ANHX	IRX1	P78414	379

IntAct

0 interactions, top by confidence:

BioGRID (1): IGF2R (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A5D7L8, A6NDY0, A6NKD2, A7E321, E9PGG2, F6SZT2, O14771, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P17564, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q2M329, Q587J8, Q5DTT8, Q5R5G8, Q5R6R8, Q5SV97, Q60465, Q62881, Q69ZB3, Q6P752, Q86V59, Q8BSI6, Q8IWY8, Q8N3D4, Q8VD63

Diamond homologs: E9PGG2, O42406, O93307, O95343, O95475, Q62233, Q94165, Q95RW8, Q9QZ28, A1YER0, A2D5H2, A6NDR6, A8K0S8, B3DM47, B4F6V6, O00470, O14770, O17894, O35317, O35984, O46339, O73916, P10842, P40424, P40425, P40426, P40427, P41778, P41779, P48731, P56661, P56662, P56666, P56667, P56668, P70178, P79937, P97367, P97368, Q15475

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1934 predictions. Top by Δscore:

Variant	Effect	Δscore
12:133225666:CAG:C	acceptor_gain	1.0000
12:133225668:G:GC	acceptor_gain	1.0000
12:133226439:C:CC	acceptor_gain	1.0000
12:133234105:TACCT:T	donor_loss	1.0000
12:133234107:C:A	donor_loss	1.0000
12:133234109:T:TA	donor_gain	1.0000
12:133234375:CACT:C	acceptor_gain	1.0000
12:133234377:CT:C	acceptor_gain	1.0000
12:133234379:C:CC	acceptor_gain	1.0000
12:133225665:CCAG:C	acceptor_gain	0.9900
12:133225667:A:T	acceptor_gain	0.9900
12:133225668:G:C	acceptor_gain	0.9900
12:133226435:TCCT:T	acceptor_gain	0.9900
12:133226436:CCTC:C	acceptor_gain	0.9900
12:133226437:CT:C	acceptor_gain	0.9900
12:133227822:AC:A	donor_gain	0.9900
12:133227823:CC:C	donor_gain	0.9900
12:133227823:CCCT:C	donor_gain	0.9900
12:133234106:A:AC	donor_gain	0.9900
12:133234106:ACCT:A	donor_gain	0.9900
12:133234107:C:CC	donor_gain	0.9900
12:133234107:CCT:C	donor_gain	0.9900
12:133234107:CCTC:C	donor_gain	0.9900
12:133234374:CCACT:C	acceptor_gain	0.9900
12:133234375:CACTC:C	acceptor_gain	0.9900
12:133234376:ACT:A	acceptor_gain	0.9900
12:133234376:ACTC:A	acceptor_loss	0.9900
12:133234377:CTC:C	acceptor_gain	0.9900
12:133234378:TC:T	acceptor_loss	0.9900
12:133234378:TCT:T	acceptor_gain	0.9900

AlphaMissense

3135 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:133227099:A:C	F185L	0.998
12:133227099:A:T	F185L	0.998
12:133227101:A:G	F185L	0.998
12:133231531:G:C	F121L	0.998
12:133231531:G:T	F121L	0.998
12:133231533:A:G	F121L	0.998
12:133227100:A:G	F185S	0.995
12:133231522:C:A	R124S	0.995
12:133231522:C:G	R124S	0.995
12:133231602:A:G	W98R	0.993
12:133231602:A:T	W98R	0.993
12:133227104:A:G	W184R	0.992
12:133227104:A:T	W184R	0.992
12:133227093:A:C	N187K	0.991
12:133227093:A:T	N187K	0.991
12:133227145:A:G	L170S	0.991
12:133231523:C:G	R124T	0.991
12:133231600:C:A	W98C	0.991
12:133231600:C:G	W98C	0.991
12:133227863:G:C	F154L	0.990
12:133227863:G:T	F154L	0.990
12:133227865:A:G	F154L	0.990
12:133231532:A:G	F121S	0.990
12:133227100:A:C	F185C	0.989
12:133231523:C:A	R124M	0.989
12:133231532:A:C	F121C	0.989
12:133231601:C:G	W98S	0.988
12:133227086:G:T	R190S	0.987
12:133227088:C:G	R189P	0.987
12:133227102:C:A	W184C	0.987

dbSNP variants (sampled 300 via entrez): RS1000065447 (12:133221497 G>C), RS1000118965 (12:133234316 G>A,C), RS1000137567 (12:133231618 C>T), RS1000154001 (12:133236441 T>C), RS1000276879 (12:133236649 G>A), RS1000349299 (12:133232107 T>A), RS1000365693 (12:133226169 G>C), RS1000580189 (12:133237370 A>G), RS1000859601 (12:133228065 A>G,T), RS1000892086 (12:133228349 G>A), RS1000932213 (12:133222560 C>T), RS1000961820 (12:133222518 C>A), RS1001046139 (12:133218152 C>CACACTGGAA), RS1001048200 (12:133218277 G>A), RS1001268018 (12:133222778 A>T)

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
GCST010002_179	Refractive error	1.000000e-12
GCST010396_116	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Clinical trials (associated diseases)

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