HOMEZ

Summary

HOMEZ (homeobox and leucine zipper encoding, HGNC:20164) is a protein-coding gene on chromosome 14q11.2, encoding Homeobox and leucine zipper protein Homez (Q8IX15). May function as a transcriptional regulator.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm.

Source: NCBI Gene 57594 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_020834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20164
Approved symbol	HOMEZ
Name	homeobox and leucine zipper encoding
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000290292
Ensembl biotype	protein_coding
OMIM	608119
Entrez	57594

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000357460, ENST00000558278, ENST00000561013, ENST00000606731, ENST00000673724

RefSeq mRNA: 1 — MANE Select: NM_020834 NM_020834

CCDS: CCDS45085

Canonical transcript exons

ENST00000357460 — 2 exons

Exon	Start	End
ENSE00001426232	23272422	23277187
ENSE00003478704	23285913	23286132

Expression profiles

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3225 / max 118.9985, expressed in 1805 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142338	12.6692	1802
142337	1.4261	898
142336	0.1500	51
142340	0.0728	5
142339	0.0044	3

Top tissues by expression

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

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2675.1	HOMEZ	HD-ZF

JASPAR matrix evidence (PMIDs): PMID:25378322

miRNA regulators (miRDB)

85 targeting HOMEZ, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
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-545-3P	99.95	70.74	2783
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778

Literature-anchored findings (GeneRIF, showing 2)

• no single gene of major effect could be convincingly identified in a sample of Indian CHD cases born to consanguineous parents. The possibility that noncoding regions of HOMEZ may harbor recessive mutations leading to CHD could not be excluded. (PMID:20422016)
• study identified two novel heterozygous missense mutations in HOMEZ gene exon-2 in isolated VSD patients in the Chinese population and have found that these two mutations resulted in alteration of the hydropathicity of the HOMEZ protein (PMID:23574532)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	homezb	ENSDARG00000024598
danio_rerio	homeza	ENSDARG00000054304
mus_musculus	Homez	ENSMUSG00000057156
rattus_norvegicus	Homez	ENSRNOG00000014887

Paralogs (3): ZHX1 (ENSG00000165156), ZHX3 (ENSG00000174306), ZHX2 (ENSG00000178764)

Protein

Protein identifiers

Homeobox and leucine zipper protein Homez — Q8IX15 (reviewed: Q8IX15)

Alternative names: Homeodomain leucine zipper-containing factor

All UniProt accessions (3): Q8IX15, A0A669KB72, U3KPW8

UniProt curated annotations — full annotation on UniProt →

Function. May function as a transcriptional regulator.

Subunit / interactions. Homodimer or heterodimer (Potential). Interacts with HOXC8.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Strongly expressed in adult testis and kidney as well as fetal lung and kidney.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IX15-1	1	yes
Q8IX15-3	2

RefSeq proteins (1): NP_065885* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR024578	Homez_homeobox_dom	Domain

Pfam: PF11569

UniProt features (31 total): helix 6, region of interest 5, compositionally biased region 4, sequence conflict 4, DNA-binding region 3, cross-link 3, modified residue 2, chain 1, splice variant 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2ECC	SOLUTION NMR
2YS9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IX15-F1	59.90	0.12

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 (5): 351, 451, 182, 200, 202

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): RNGTGGGC_UNKNOWN, TAATAAT_MIR126, AFP1_Q6, AACTTT_UNKNOWN, ACEVEDO_LIVER_CANCER_UP, TAL1BETAE47_01, GOCC_NUCLEOLUS, GSE13522_WT_VS_IFNG_KO_SKIN_DN, TAL1BETAITF2_01, RORA2_01, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, CACBINDINGPROTEIN_Q6, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_DN, MIR4795_3P

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (3): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOMEZ	HOXC8	P31273	716
HOMEZ	LRIT1	Q9P2V4	527
HOMEZ	DCP1B	Q8IZD4	461
HOMEZ	DMBX1	Q8NFW5	419
HOMEZ	FOXB1	Q99853	408
HOMEZ	HDX	Q7Z353	394
HOMEZ	RPL7L1	Q6DKI1	379
HOMEZ	BARHL1	Q9BZE3	377
HOMEZ	ZHX1	Q9UKY1	377
HOMEZ	TRAPPC12	Q8WVT3	370
HOMEZ	OR13A1	Q8NGR1	357
HOMEZ	PKNOX2	Q96KN3	355
HOMEZ	OR5P3	Q8WZ94	352
HOMEZ	ZHX3	Q9H4I2	349
HOMEZ	CIMIP5	Q96LR7	349

IntAct

41 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
rep	HOMEZ	psi-mi:“MI:0915”(physical association)	0.600
HOMEZ	SMYD1	psi-mi:“MI:0915”(physical association)	0.550
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
HOMEZ	CPEB4	psi-mi:“MI:0914”(association)	0.530
ZMYND11	HOMEZ	psi-mi:“MI:0407”(direct interaction)	0.440
HOMEZ	MED18	psi-mi:“MI:0915”(physical association)	0.370
HOMEZ	LNX1	psi-mi:“MI:0915”(physical association)	0.370
HOMEZ		psi-mi:“MI:0915”(physical association)	0.370
HOMEZ	SMARCB1	psi-mi:“MI:0915”(physical association)	0.370
Bap1	RNF40	psi-mi:“MI:0914”(association)	0.350
Fgfr1	METAP2	psi-mi:“MI:0914”(association)	0.350
	ZNF316	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
HOMEZ	KCNQ1	psi-mi:“MI:0914”(association)	0.350
GTF2IRD1	HOMEZ	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (182): HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid), HOMEZ (Two-hybrid)

ESM2 similar proteins: A0JNJ4, A2APF3, A2VDT4, F6WEQ6, G5E869, O14753, O15015, O88282, O88286, O95785, P52746, P98168, P98169, Q05516, Q2I689, Q2MHN3, Q3U288, Q3U381, Q4R8S8, Q504L7, Q5R4P8, Q6NS86, Q6NV66, Q6ZN55, Q6ZPY5, Q80W88, Q80Z36, Q8BLK9, Q8BY46, Q8C8V1, Q8CIV7, Q8IX15, Q8K3E9, Q8N1G0, Q8N1W2, Q8N895, Q90W33, Q92610, Q96JB3, Q9BRP0

Diamond homologs: A1YF22, A1YG99, A2T771, A2T7S4, P70121, Q5R7F2, Q80VX4, Q80Z36, Q8C0C0, Q8C0Q2, Q8IX15, Q8R515, Q9H4I2, Q9UKY1, Q9Y6X8, Q80W88, Q8K3E9, Q61321, Q9UIU6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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
Activation of BAD and translocation to mitochondria	5	135.9×	1e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	120.0×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	120.0×	2e-08
Activation of BH3-only proteins	5	88.7×	7e-08
RHO GTPases activate PKNs	5	56.6×	7e-07
Intrinsic Pathway for Apoptosis	5	52.3×	9e-07
Transcriptional and post-translational regulation of MITF-M expression and activity	5	31.9×	9e-06
SARS-CoV-1-host interactions	5	31.4×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	5	13.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

901 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23272821:A:AG	acceptor_gain	0.9900
14:23272822:G:GG	acceptor_gain	0.9900
14:23277185:TAG:T	acceptor_gain	0.9900
14:23277188:C:CC	acceptor_gain	0.9900
14:23285908:CTCA:C	donor_loss	0.9800
14:23285909:TCACC:T	donor_loss	0.9800
14:23285910:C:CC	donor_loss	0.9800
14:23285911:A:AC	donor_gain	0.9800
14:23285912:C:CA	donor_loss	0.9800
14:23285912:C:CC	donor_gain	0.9800
14:23285912:CCG:C	donor_gain	0.9800
14:23299537:CCCTT:C	acceptor_gain	0.9800
14:23299538:CCTTC:C	acceptor_gain	0.9800
14:23299539:CTT:C	acceptor_gain	0.9800
14:23299572:A:C	acceptor_gain	0.9800
14:23272815:T:TA	acceptor_gain	0.9700
14:23272817:CTGCA:C	acceptor_loss	0.9700
14:23272818:TGCA:T	acceptor_loss	0.9700
14:23272819:GCA:G	acceptor_loss	0.9700
14:23272820:CAGAC:C	acceptor_loss	0.9700
14:23272821:AGACT:A	acceptor_loss	0.9700
14:23272822:G:C	acceptor_loss	0.9700
14:23272822:GA:G	acceptor_gain	0.9600
14:23285437:TCTAA:T	donor_gain	0.9600
14:23272822:GACT:G	acceptor_gain	0.9500
14:23277185:TAGC:T	acceptor_loss	0.9500
14:23277187:GC:G	acceptor_loss	0.9500
14:23282744:T:A	donor_gain	0.9500
14:23299542:C:CC	acceptor_gain	0.9500
14:23277190:G:C	acceptor_loss	0.9400

AlphaMissense

3567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23276019:C:A	W403C	1.000
14:23276019:C:G	W403C	1.000
14:23276021:A:G	W403R	1.000
14:23276021:A:T	W403R	1.000
14:23276116:A:G	L371P	1.000
14:23276116:A:T	L371H	1.000
14:23276886:C:A	W114C	1.000
14:23276886:C:G	W114C	1.000
14:23276888:A:G	W114R	1.000
14:23276888:A:T	W114R	1.000
14:23276909:G:T	R107S	1.000
14:23276920:A:G	F103S	1.000
14:23276924:A:G	W102R	1.000
14:23276924:A:T	W102R	1.000
14:23275976:A:G	W418R	0.999
14:23275976:A:T	W418R	0.999
14:23276006:G:T	R408S	0.999
14:23276011:T:A	D406V	0.999
14:23276011:T:C	D406G	0.999
14:23276014:C:T	G405D	0.999
14:23276016:A:C	F404L	0.999
14:23276016:A:T	F404L	0.999
14:23276017:A:C	F404C	0.999
14:23276017:A:G	F404S	0.999
14:23276018:A:G	F404L	0.999
14:23276020:C:G	W403S	0.999
14:23276044:A:G	L395S	0.999
14:23276062:A:G	L389S	0.999
14:23276088:C:A	W380C	0.999
14:23276088:C:G	W380C	0.999

dbSNP variants (sampled 300 via entrez): RS1000044977 (14:23274675 A>C), RS1000078309 (14:23282744 T>C), RS1000168744 (14:23273942 A>G), RS1000323310 (14:23280082 G>A), RS1000342342 (14:23285979 C>G), RS1000557615 (14:23280898 T>C), RS1000591853 (14:23280353 T>C), RS1000810161 (14:23284116 G>C), RS1001161920 (14:23274906 A>C), RS1001572574 (14:23274887 C>T), RS1002447530 (14:23275214 A>G), RS1002494800 (14:23286764 G>A,C), RS1002831280 (14:23287286 G>A,C), RS1002926997 (14:23272213 C>G,T), RS1003111971 (14:23277995 C>A)

Disease associations

OMIM: gene MIM:608119 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST007096_169	Pulse pressure	2.000000e-12
GCST007097_35	Pulse pressure	2.000000e-08
GCST007097_36	Pulse pressure	5.000000e-08
GCST007099_33	Systolic blood pressure	3.000000e-07
GCST008839_56	Height	9.000000e-14
GCST012227_600	Hip circumference adjusted for BMI	2.000000e-11
GCST90002385_20	High light scatter reticulocyte count	1.000000e-15
GCST90002386_163	High light scatter reticulocyte percentage of red cells	3.000000e-16
GCST90002395_166	Mean platelet volume	3.000000e-13
GCST90002405_363	Reticulocyte count	2.000000e-12
GCST90011900_110	Serum alkaline phosphatase levels	5.000000e-10
GCST90020028_1231	Hip circumference adjusted for BMI	2.000000e-14
GCST90020028_1232	Hip circumference adjusted for BMI	4.000000e-08
GCST90020028_1233	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0008039	BMI-adjusted hip circumference
EFO:0007986	reticulocyte count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
bisphenol A	affects cotreatment, increases methylation, increases expression	2
entinostat	decreases expression, affects cotreatment	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases abundance, increases expression	1
ferrous chloride	decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Panobinostat	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects expression	1
Manganese	increases abundance, increases expression	1
Oxygen	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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