REC114

Summary

REC114 (REC114 meiotic recombination protein, HGNC:25065) is a protein-coding gene on chromosome 15q24.1, encoding Meiotic recombination protein REC114 (Q7Z4M0). Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination.

The protein encoded by this gene is orthologous to the mouse meiotic recombination protein REC114, which is involved in DNA double-strand break formation during meiosis. The encoded protein is conserved in most eukaryotes and was first discovered and characterized in yeast.

Source: NCBI Gene 283677 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte maturation defect 10 (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 59 total — 2 pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_001042367

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25065
Approved symbol	REC114
Name	REC114 meiotic recombination protein
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	LOC283677, FLJ27520, FLJ36860, FLJ44083, CT147
Ensembl gene	ENSG00000183324
Ensembl biotype	protein_coding
OMIM	618421
Entrez	283677

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000331090, ENST00000560581

RefSeq mRNA: 2 — MANE Select: NM_001042367 NM_001042367, NM_001348772

CCDS: CCDS45296, CCDS86474

Canonical transcript exons

ENST00000331090 — 6 exons

Exon	Start	End
ENSE00001295789	73473832	73473921
ENSE00001308393	73556302	73556391
ENSE00001317513	73540485	73540568
ENSE00001330489	73550938	73551150
ENSE00002537921	73443164	73443344
ENSE00002556865	73559752	73560013

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 95.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0641 / max 50.5215, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147602	0.0641	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.95	gold quality
secondary oocyte	CL:0000655	93.19	gold quality
right testis	UBERON:0004534	91.62	gold quality
left testis	UBERON:0004533	91.52	gold quality
sperm	CL:0000019	90.91	gold quality
testis	UBERON:0000473	89.46	gold quality
adult organism	UBERON:0007023	86.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.95	gold quality
tibialis anterior	UBERON:0001385	78.96	silver quality
right atrium auricular region	UBERON:0006631	76.96	gold quality
cardiac atrium	UBERON:0002081	76.45	gold quality
left ventricle myocardium	UBERON:0006566	74.38	gold quality
ileal mucosa	UBERON:0000331	67.49	gold quality
deltoid	UBERON:0001476	66.08	silver quality
buccal mucosa cell	CL:0002336	65.92	gold quality
pancreatic ductal cell	CL:0002079	64.86	silver quality
parotid gland	UBERON:0001831	64.63	gold quality
apex of heart	UBERON:0002098	63.51	gold quality
biceps brachii	UBERON:0001507	61.73	gold quality
oral cavity	UBERON:0000167	59.60	gold quality
heart	UBERON:0000948	59.51	gold quality
upper leg skin	UBERON:0004262	59.43	gold quality
esophagus squamous epithelium	UBERON:0006920	59.13	gold quality
calcaneal tendon	UBERON:0003701	58.66	gold quality
endothelial cell	CL:0000115	57.81	gold quality
cartilage tissue	UBERON:0002418	57.79	gold quality
gingiva	UBERON:0001828	57.73	gold quality
skin of hip	UBERON:0001554	56.70	silver quality
gingival epithelium	UBERON:0001949	56.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF699

Literature-anchored findings (GeneRIF, showing 3)

• In Japanese individuals, combined genotyping for the associated variants thus far identified; that is, HLA-A*02:06, TLR3 rs3775296 T/T and Rec114 rs16957893 CG, may help to predict the risk for cold medicine-related Stevens-Johnson syndrome /TEN with severe ocular complications (PMID:28100913)
• Homozygous mutations in REC114 cause female infertility characterised by multiple pronuclei formation and early embryonic arrest. (PMID:31704776)
• A bi-allelic REC114 loss-of-function variant causes meiotic arrest and nonobstructive azoospermia. (PMID:38148155)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rec114	ENSDARG00000069781
mus_musculus	Rec114	ENSMUSG00000074269
rattus_norvegicus	Rec114	ENSRNOG00000009332

Protein

Protein identifiers

Meiotic recombination protein REC114 — Q7Z4M0 (reviewed: Q7Z4M0)

All UniProt accessions (2): H0YKR2, Q7Z4M0

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 IHO1 and MEI4, which activates DSBs formation in unsynapsed regions, an essential step to ensure completion of synapsis. Required for spermatogenesis. Required for oogenesis.

Subunit / interactions. Part of the MCD recombinosome complex, at least composed of IHO1, REC114 and MEI4. Forms a complex with MEI4; the interaction is required for MEI4 stability. Interacts (via C-terminal domain) with MEI4 (via N-terminal domain). Interacts with IHO1. Interacts with ANKRD31; the interaction is direct.

Subcellular location. Chromosome.

Disease relevance. Oocyte/zygote/embryo maturation arrest 10 (OZEMA10) [MIM:619176] An autosomal recessive infertility disorder due to abnormal fertilization of mature oocytes, with development of multiple pronuclei or absent pronucleus, and early embryonic arrest. The gene represented in this entry is involved in disease pathogenesis.

Similarity. Belongs to the REC114 family.

RefSeq proteins (2): NP_001035826, NP_001335701 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029168	REC114L	Family

Pfam: PF15165

UniProt features (6 total): sequence variant 3, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4M0-F1	73.71	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 51 (showing top): GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_MEIOTIC_CELL_CYCLE, GOBP_CELL_CYCLE_PROCESS, GOBP_DNA_METABOLIC_PROCESS, GOBP_DNA_RECOMBINATION, GOCC_NUCLEAR_CHROMOSOME, GOCC_CONDENSED_NUCLEAR_CHROMOSOME, PILON_KLF1_TARGETS_UP, GOBP_MEIOTIC_DNA_DOUBLE_STRAND_BREAK_FORMATION, MADAN_DPPA4_TARGETS

GO Biological Process (6): DNA recombination (GO:0006310), spermatogenesis (GO:0007283), meiotic DNA double-strand break formation (GO:0042138), oogenesis (GO:0048477), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321)

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

GO Cellular Component (1): chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
developmental process involved in reproduction	1
male gamete generation	1
meiosis I cell cycle process	1
germ cell development	1
female gamete generation	1
cellular developmental process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
binding	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1176 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REC114	MEI4	A8MW99	997
REC114	CD151	P48509	983
REC114	IHO1	Q8IYA8	953
REC114	ANKRD31	Q8N7Z5	940
REC114	MEI1	Q5TIA1	906
REC114	SPO11	Q9Y5K1	866
REC114	TOP6BL	Q8N6T0	824
REC114	HORMAD1	Q86X24	719
REC114	SKIC8	Q9GZS3	690
REC114	REC8	O95072	673
REC114	MSH4	O15457	667
REC114	NEK9	Q8TD19	641
REC114	ADARB1	P78555	641
REC114	PRDM9	Q9NQV7	627
REC114	HFM1	A2PYH4	620

IntAct

5 interactions, top by confidence:

A	B	Type	Score
REC114	MEI4	psi-mi:“MI:0915”(physical association)	0.590
MEI4	REC114	psi-mi:“MI:0915”(physical association)	0.590
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (4): REC114 (Affinity Capture-MS), REC114 (Co-fractionation), REC114 (Co-fractionation), REC114 (Co-fractionation)

ESM2 similar proteins: A0A1L8ENT6, A2BGP7, A2CJ06, B1H1W9, F6RRD7, O00124, O55036, P54274, Q1LV50, Q1LWH4, Q1T7B8, Q28HU3, Q3KNJ2, Q3U1D0, Q3US16, Q4KLN8, Q4V832, Q5I0E6, Q5I2W8, Q5NVA9, Q5RA37, Q5RET9, Q5XI46, Q5ZIN2, Q6AYI4, Q6DRL4, Q6IQ49, Q6IRN0, Q6NV18, Q6P1H6, Q7Z2Z1, Q7Z4M0, Q8BJW7, Q8BKT3, Q8BMG1, Q8BMI4, Q8BQ33, Q8IXW5, Q8K1J5, Q8VC34

Diamond homologs: Q7Z4M0, Q9CWH4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	45
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
996125	NM_001042367.2(REC114):c.397T>G (p.Cys133Gly)	Pathogenic
996126	NM_001042367.2(REC114):c.546+5G>A	Pathogenic

SpliceAI

1471 predictions. Top by Δscore:

Variant	Effect	Δscore
15:73540581:C:G	donor_gain	1.0000
15:73551114:G:T	donor_gain	1.0000
15:73551151:G:GG	donor_gain	1.0000
15:73463303:GC:G	donor_gain	0.9900
15:73473830:A:G	acceptor_gain	0.9900
15:73483847:G:GT	donor_gain	0.9900
15:73540107:A:G	donor_gain	0.9900
15:73540576:T:G	donor_gain	0.9900
15:73551148:GGA:G	donor_gain	0.9900
15:73551149:GA:G	donor_gain	0.9900
15:73551149:GAG:G	donor_gain	0.9900
15:73556300:A:AG	acceptor_gain	0.9900
15:73556301:G:GG	acceptor_gain	0.9900
15:73559750:A:AG	acceptor_gain	0.9900
15:73559751:G:GG	acceptor_gain	0.9900
15:73443342:AAGGT:A	donor_loss	0.9800
15:73443343:AG:A	donor_loss	0.9800
15:73443344:GG:G	donor_loss	0.9800
15:73443345:GT:G	donor_loss	0.9800
15:73443346:T:G	donor_loss	0.9800
15:73550936:A:C	acceptor_loss	0.9800
15:73551114:G:GT	donor_gain	0.9800
15:73551146:CTGGA:C	donor_gain	0.9800
15:73551147:TGGAG:T	donor_loss	0.9800
15:73551148:GGAGT:G	donor_loss	0.9800
15:73551152:TAAG:T	donor_loss	0.9800
15:73551153:AAG:A	donor_loss	0.9800
15:73551154:A:AC	donor_loss	0.9800
15:73551155:G:GG	donor_gain	0.9800
15:73555198:T:TA	donor_gain	0.9800

AlphaMissense

1703 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:73550966:T:C	F121S	0.997
15:73550954:T:C	F117S	0.993
15:73550965:T:C	F121L	0.993
15:73550967:C:A	F121L	0.993
15:73550967:C:G	F121L	0.993
15:73550957:G:C	R118P	0.992
15:73540546:T:C	L104P	0.990
15:73559888:T:C	L258P	0.988
15:73540498:T:A	L88H	0.987
15:73443246:T:A	W21R	0.986
15:73443246:T:C	W21R	0.986
15:73473899:T:A	I76N	0.986
15:73540519:T:C	L95S	0.986
15:73550953:T:C	F117L	0.986
15:73550955:T:A	F117L	0.986
15:73550955:T:G	F117L	0.986
15:73550966:T:G	F121C	0.985
15:73551010:T:C	C136R	0.985
15:73559854:T:C	F247L	0.985
15:73559856:C:A	F247L	0.985
15:73559856:C:G	F247L	0.985
15:73559836:T:C	C241R	0.984
15:73551012:T:G	C136W	0.983
15:73443248:G:C	W21C	0.982
15:73443248:G:T	W21C	0.982
15:73473887:G:T	G72V	0.982
15:73473869:T:C	L66P	0.981
15:73540492:T:C	F86S	0.981
15:73551003:C:G	C133W	0.981
15:73559855:T:C	F247S	0.981

dbSNP variants (sampled 300 via entrez): RS1000068084 (15:73443584 A>G), RS1000084866 (15:73516678 A>G), RS1000121537 (15:73443874 TAG>T), RS1000143976 (15:73502169 A>G,T), RS1000150700 (15:73457173 G>A), RS1000229782 (15:73505646 C>A), RS1000258903 (15:73502422 T>G), RS1000261292 (15:73486317 C>T), RS1000280816 (15:73455317 G>T), RS1000326659 (15:73557132 C>T), RS1000347189 (15:73492260 C>T), RS1000358947 (15:73463215 C>T), RS1000396329 (15:73520494 T>C,G), RS1000408264 (15:73545614 G>A), RS1000433433 (15:73523821 C>CTAG)

Disease associations

OMIM: gene MIM:618421 | disease phenotypes: MIM:619176

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte maturation defect 10	Strong	Autosomal recessive

Mondo (1): oocyte maturation defect 10 (MONDO:0030925)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003581	Adult onset
HP:0005268	Miscarriage
HP:0008222	Female infertility
HP:0033712	Repeated implantation failure
HP:4000008	Formation of multiple pronuclei during fertilization

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004072_1	Cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with severe ocular complications	2.000000e-08
GCST005956_11	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_52	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST006061_48	Atrial fibrillation	2.000000e-27
GCST006061_62	Atrial fibrillation	1.000000e-27
GCST007277_20	Tourette syndrome	7.000000e-06
GCST007431_51	Lung function (FEV1/FVC)	7.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006997	response to cold medicine
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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