IHO1

Summary

IHO1 (interactor of HORMAD1 1, HGNC:27945) is a protein-coding gene on chromosome 3p21.31, encoding Interactor of HORMAD1 protein 1 (Q8IYA8). Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination.

Predicted to be involved in several processes, including meiosis I cell cycle process; regulation of homologous chromosome segregation; and spermatogenesis. Predicted to be located in chromosome. Predicted to be active in condensed nuclear chromosome.

Source: NCBI Gene 339834 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_001135197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27945
Approved symbol	IHO1
Name	interactor of HORMAD1 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25320, CT74, LELA1
Ensembl gene	ENSG00000173421
Ensembl biotype	protein_coding
OMIM	619190
Entrez	339834

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296449, ENST00000366429, ENST00000438782, ENST00000452691, ENST00000493870, ENST00000909984, ENST00000961111

RefSeq mRNA: 2 — MANE Select: NM_001135197 NM_001135197, NM_178173

CCDS: CCDS33755

Canonical transcript exons

ENST00000452691 — 8 exons

Exon	Start	End
ENSE00001080962	49241226	49241389
ENSE00001080965	49244404	49244452
ENSE00001204715	49244646	49244733
ENSE00001204734	49255390	49255493
ENSE00001335195	49236548	49236722
ENSE00001498333	49211766	49211836
ENSE00001643409	49199498	49199573
ENSE00003851164	49256134	49258106

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 91.65.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8151 / max 86.1572, expressed in 631 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36617	1.2045	546
36618	0.6106	299

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	91.65	gold quality
right testis	UBERON:0004534	90.92	gold quality
testis	UBERON:0000473	88.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.70	gold quality
stromal cell of endometrium	CL:0002255	73.02	gold quality
buccal mucosa cell	CL:0002336	72.90	silver quality
hindlimb stylopod muscle	UBERON:0004252	72.34	gold quality
left ovary	UBERON:0002119	71.20	gold quality
sperm	CL:0000019	70.78	gold quality
endothelial cell	CL:0000115	70.71	gold quality
tendon of biceps brachii	UBERON:0008188	70.07	gold quality
right ovary	UBERON:0002118	69.37	gold quality
apex of heart	UBERON:0002098	69.19	gold quality
ovary	UBERON:0000992	68.68	gold quality
adrenal tissue	UBERON:0018303	67.62	gold quality
right adrenal gland cortex	UBERON:0035827	66.98	gold quality
adult organism	UBERON:0007023	65.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	65.55	gold quality
right adrenal gland	UBERON:0001233	65.10	gold quality
left adrenal gland	UBERON:0001234	64.75	gold quality
tendon	UBERON:0000043	64.52	gold quality
adrenal gland	UBERON:0002369	64.16	gold quality
smooth muscle tissue	UBERON:0001135	64.13	gold quality
omental fat pad	UBERON:0010414	63.93	gold quality
peritoneum	UBERON:0002358	63.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.53	gold quality
lower esophagus	UBERON:0013473	63.50	gold quality
descending thoracic aorta	UBERON:0002345	63.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	63.22	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.57
E-MTAB-7606	no	2.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting IHO1, 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-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6071	99.16	67.77	1780

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc36	ENSDARG00000097704
mus_musculus	Iho1	ENSMUSG00000047220
rattus_norvegicus	Iho1	ENSRNOG00000048919

Protein

Protein identifiers

Interactor of HORMAD1 protein 1 — Q8IYA8 (reviewed: Q8IYA8)

Alternative names: Cancer/testis antigen 74, Coiled-coil domain-containing protein 36

All UniProt accessions (1): Q8IYA8

UniProt curated annotations — full annotation on UniProt →

Function. Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination. Probably acts by forming a complex with MEI4 and REC114, which activates DSBs formation in unsynapsed regions, an essential step to ensure completion of synapsis. Not required for HORMAD1 functions in pairing-independent synaptonemal complex formation, ATR recruitment to unsynapsed axes, meiotic silencing of unsynapsed chromatin (MSUC) or meiotic surveillance.

Subunit / interactions. Part of the MCD recombinosome complex, at least composed of IHO1, REC114 and MEI4. Interacts with REC114. Interacts with MEI4. Interacts with HORMAD1. Interacts with ANKRD31.

Subcellular location. Chromosome.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IYA8-1	1	yes
Q8IYA8-2	2
Q8IYA8-3	3

RefSeq proteins (2): NP_001128669, NP_835467 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031529	IHO1	Family

Pfam: PF15771

UniProt features (14 total): splice variant 4, coiled-coil region 3, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYA8-F1	55.17	0.22

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 (2): 588, 589

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (8): DNA recombination (GO:0006310), homologous chromosome pairing at meiosis (GO:0007129), spermatogenesis (GO:0007283), meiotic DNA double-strand break formation (GO:0042138), oogenesis (GO:0048477), regulation of homologous chromosome segregation (GO:0060629), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): condensed nuclear chromosome (GO:0000794), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
homologous chromosome segregation	2
chromosome organization involved in meiotic cell cycle	1
developmental process involved in reproduction	1
male gamete generation	1
meiosis I cell cycle process	1
germ cell development	1
female gamete generation	1
regulation of chromosome segregation	1
regulation of reproductive process	1
cellular developmental process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
binding	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IHO1	REC114	Q7Z4M0	953
IHO1	HORMAD1	Q86X24	949
IHO1	MEI4	A8MW99	913
IHO1	CXXC1	Q9P0U4	904
IHO1	ANKRD31	Q8N7Z5	870
IHO1	MEI1	Q5TIA1	805
IHO1	SPO11	Q9Y5K1	802
IHO1	TOP6BL	Q8N6T0	800
IHO1	PRDM9	Q9NQV7	778
IHO1	CD151	P48509	672
IHO1	PRR35	P0CG20	592
IHO1	SYCP1	Q15431	571
IHO1	SYCP3	Q8IZU3	570
IHO1	HORMAD2	Q8N7B1	548
IHO1	RAD21L1	Q9H4I0	545

IntAct

324 interactions, top by confidence:

A	B	Type	Score
FKBP6	IHO1	psi-mi:“MI:0915”(physical association)	0.830
IHO1	FKBP6	psi-mi:“MI:0915”(physical association)	0.830
IHO1	PRKAB2	psi-mi:“MI:0915”(physical association)	0.760
PRKAB2	IHO1	psi-mi:“MI:0915”(physical association)	0.760
IHO1	ABI2	psi-mi:“MI:0915”(physical association)	0.740
ABI2	IHO1	psi-mi:“MI:0915”(physical association)	0.740
GYS1	IHO1	psi-mi:“MI:0915”(physical association)	0.720
DYNLL1	IHO1	psi-mi:“MI:0915”(physical association)	0.720
LONRF1	IHO1	psi-mi:“MI:0915”(physical association)	0.720
IHO1	KANK2	psi-mi:“MI:0915”(physical association)	0.720
TTC19	IHO1	psi-mi:“MI:0915”(physical association)	0.720
NGB	IHO1	psi-mi:“MI:0915”(physical association)	0.720
AIRIM	IHO1	psi-mi:“MI:0915”(physical association)	0.720
IHO1	CDC23	psi-mi:“MI:0915”(physical association)	0.720
IHO1	USP20	psi-mi:“MI:0915”(physical association)	0.720
IHO1	GYS1	psi-mi:“MI:0915”(physical association)	0.720
IHO1	DYNLL1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (118): CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid), CCDC36 (Two-hybrid)

ESM2 similar proteins: A2A7Y5, A2AFS9, A2AIW0, A6NFA0, A6NMK8, A9JRX0, B2RQL2, C3VD30, P54257, Q0VET5, Q0VG85, Q14B48, Q2M243, Q2YDE2, Q3V036, Q3V0C3, Q3V0M2, Q4R739, Q5E9L4, Q5PQS2, Q5R9L2, Q60664, Q6AYH0, Q6AYP4, Q6DF94, Q6GQV1, Q6NZK5, Q6P1D7, Q6ZRS4, Q6ZVD7, Q70YC5, Q7L3B6, Q7M6U3, Q7Z572, Q86WZ0, Q8BG89, Q8CCC3, Q8CCG1, Q8CH09, Q8IYA8

Diamond homologs: Q6PDM4, Q8IYA8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	IHO1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1468 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49236719:GGAG:G	donor_gain	1.0000
3:49236720:GAGG:G	donor_gain	1.0000
3:49236721:AGGT:A	donor_loss	1.0000
3:49236723:GTGA:G	donor_loss	1.0000
3:49236724:T:A	donor_loss	1.0000
3:49241217:A:AG	acceptor_gain	1.0000
3:49241221:AACAG:A	acceptor_gain	1.0000
3:49241222:A:G	acceptor_gain	1.0000
3:49241222:ACAG:A	acceptor_gain	1.0000
3:49241224:A:AG	acceptor_gain	1.0000
3:49241224:A:AT	acceptor_loss	1.0000
3:49241224:AG:A	acceptor_gain	1.0000
3:49241224:AGG:A	acceptor_gain	1.0000
3:49241224:AGGGT:A	acceptor_gain	1.0000
3:49241225:G:GA	acceptor_gain	1.0000
3:49241225:GG:G	acceptor_gain	1.0000
3:49241225:GGG:G	acceptor_gain	1.0000
3:49241225:GGGT:G	acceptor_gain	1.0000
3:49241225:GGGTG:G	acceptor_gain	1.0000
3:49241385:GACAG:G	donor_gain	1.0000
3:49241386:ACAG:A	donor_gain	1.0000
3:49244645:G:GT	acceptor_gain	1.0000
3:49244729:GACAT:G	donor_gain	1.0000
3:49244734:G:GG	donor_gain	1.0000
3:49255388:A:AG	acceptor_gain	1.0000
3:49255389:G:GG	acceptor_gain	1.0000
3:49255389:GTACA:G	acceptor_gain	1.0000
3:49255491:GCT:G	donor_gain	1.0000
3:49255492:CT:C	donor_gain	1.0000
3:49255492:CTGT:C	donor_loss	1.0000

AlphaMissense

3952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49236618:T:C	F43L	0.967
3:49236620:T:A	F43L	0.967
3:49236620:T:G	F43L	0.967
3:49236630:T:C	F47L	0.967
3:49236632:C:A	F47L	0.967
3:49236632:C:G	F47L	0.967
3:49241349:T:C	F119L	0.964
3:49241351:T:A	F119L	0.964
3:49241351:T:G	F119L	0.964
3:49236612:T:C	F41L	0.962
3:49236614:C:A	F41L	0.962
3:49236614:C:G	F41L	0.962
3:49211796:T:A	W6R	0.960
3:49211796:T:C	W6R	0.960
3:49257175:T:C	F560L	0.955
3:49257177:C:A	F560L	0.955
3:49257177:C:G	F560L	0.955
3:49236622:G:A	G44E	0.952
3:49236600:A:C	S37R	0.948
3:49236602:T:A	S37R	0.948
3:49236602:T:G	S37R	0.948
3:49236613:T:C	F41S	0.948
3:49244691:A:C	S164R	0.948
3:49244693:C:A	S164R	0.948
3:49244693:C:G	S164R	0.948
3:49241250:T:G	Y86D	0.946
3:49257259:A:C	S588R	0.946
3:49257261:C:A	S588R	0.946
3:49257261:C:G	S588R	0.946
3:49256168:T:C	L224P	0.941

dbSNP variants (sampled 300 via entrez): RS1000045735 (3:49254370 G>A), RS1000089295 (3:49226239 A>G,T), RS1000143530 (3:49239152 A>G), RS1000196326 (3:49223309 C>T), RS1000201112 (3:49226202 C>T), RS1000242397 (3:49220327 G>A), RS1000317814 (3:49220145 G>A), RS1000343409 (3:49202388 C>T), RS1000355289 (3:49235130 G>A), RS1000525689 (3:49221927 G>A), RS1000536983 (3:49244501 A>G), RS1000745799 (3:49237639 A>G), RS1000847572 (3:49213654 C>G,T), RS1000871693 (3:49231103 T>C,G), RS1000900397 (3:49194802 G>A)

Disease associations

OMIM: gene MIM:619190 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST004602_128	Mean corpuscular volume	1.000000e-11
GCST004630_116	Mean corpuscular hemoglobin	8.000000e-12
GCST008163_589	Height	3.000000e-06
GCST008357_20	Mood instability	4.000000e-11
GCST008526_26	Coffee consumption	2.000000e-06
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0008475	mood instability measurement
EFO:0006781	coffee consumption measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	increases expression	2
bisphenol A	affects cotreatment, decreases methylation	1
bromovanin	decreases expression	1
bisphenol S	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Testosterone	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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