MEI1

Summary

MEI1 (meiotic double-stranded break formation protein 1, HGNC:28613) is a protein-coding gene on chromosome 22q13.2, encoding Meiosis inhibitor protein 1 (Q5TIA1). Required for normal meiotic chromosome synapsis.

Predicted to be involved in meiosis I. Predicted to act upstream of or within germ cell development; meiotic nuclear division; and meiotic spindle organization. Implicated in gestational trophoblastic neoplasm.

Source: NCBI Gene 150365 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hydatidiform mole, recurrent, 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 233 total — 3 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_152513

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28613
Approved symbol	MEI1
Name	meiotic double-stranded break formation protein 1
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC40042, SPATA38
Ensembl gene	ENSG00000167077
Ensembl biotype	protein_coding
OMIM	608797
Entrez	150365

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding_CDS_not_defined, 5 protein_coding, 4 retained_intron

ENST00000401548, ENST00000403492, ENST00000423900, ENST00000460702, ENST00000462246, ENST00000462450, ENST00000473736, ENST00000476614, ENST00000476893, ENST00000482055, ENST00000484966, ENST00000487535, ENST00000492484, ENST00000498456, ENST00000540833, ENST00000651135, ENST00000890163

RefSeq mRNA: 1 — MANE Select: NM_152513 NM_152513

CCDS: CCDS46718

Canonical transcript exons

ENST00000401548 — 31 exons

Exon	Start	End
ENSE00001925489	41799254	41799454
ENSE00001954048	41699503	41699712
ENSE00003458521	41793829	41793910
ENSE00003461920	41758365	41758533
ENSE00003466818	41718071	41718274
ENSE00003475368	41784608	41784783
ENSE00003476222	41752591	41752651
ENSE00003476631	41781284	41781394
ENSE00003481547	41776102	41776267
ENSE00003504964	41703331	41703454
ENSE00003508041	41781685	41781845
ENSE00003513520	41743080	41743194
ENSE00003523779	41778708	41778812
ENSE00003524069	41784339	41784420
ENSE00003528194	41745885	41746026
ENSE00003531999	41730521	41730637
ENSE00003533832	41729665	41729779
ENSE00003543901	41744973	41745064
ENSE00003546118	41748107	41748218
ENSE00003547292	41716041	41716146
ENSE00003552644	41732469	41732603
ENSE00003556527	41795735	41795847
ENSE00003560411	41705504	41705554
ENSE00003562965	41763174	41763321
ENSE00003633904	41723943	41724073
ENSE00003644054	41714002	41714075
ENSE00003677969	41732245	41732344
ENSE00003678775	41795411	41795542
ENSE00003687019	41794371	41794477
ENSE00003692500	41753949	41754046
ENSE00003694377	41770686	41770961

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 95.70.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5949 / max 439.1957, expressed in 650 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192504	4.4455	540
192503	0.6379	280
192505	0.2831	130
192498	0.1364	27
192500	0.0363	20
192499	0.0331	15
192501	0.0167	9
192502	0.0059	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	95.70	gold quality
right testis	UBERON:0004534	94.77	gold quality
granulocyte	CL:0000094	94.15	gold quality
left testis	UBERON:0004533	93.80	gold quality
testis	UBERON:0000473	90.12	gold quality
spleen	UBERON:0002106	89.80	gold quality
vermiform appendix	UBERON:0001154	88.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.37	gold quality
blood	UBERON:0000178	87.12	gold quality
lymph node	UBERON:0000029	85.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.13	gold quality
bone marrow	UBERON:0002371	82.81	gold quality
upper arm skin	UBERON:0004263	82.75	gold quality
leukocyte	CL:0000738	82.10	gold quality
rectum	UBERON:0001052	82.10	gold quality
caecum	UBERON:0001153	82.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.84	gold quality
monocyte	CL:0000576	81.04	gold quality
colonic epithelium	UBERON:0000397	80.87	gold quality
minor salivary gland	UBERON:0001830	80.45	gold quality
mucosa of transverse colon	UBERON:0004991	80.29	gold quality
tonsil	UBERON:0002372	79.87	gold quality
small intestine	UBERON:0002108	79.54	gold quality
pancreatic ductal cell	CL:0002079	79.09	silver quality
transverse colon	UBERON:0001157	78.06	gold quality
mouth mucosa	UBERON:0003729	77.89	gold quality
saliva-secreting gland	UBERON:0001044	77.48	gold quality
upper lobe of left lung	UBERON:0008952	77.25	gold quality
ileal mucosa	UBERON:0000331	76.21	silver quality
upper lobe of lung	UBERON:0008948	74.77	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	38.45
E-MTAB-8410	yes	35.33
E-ANND-3	yes	26.21
E-HCAD-11	yes	21.88
E-HCAD-1	yes	11.29
E-MTAB-10553	yes	9.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting MEI1, 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-1305	99.91	71.43	3443
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-4486	96.96	60.61	931

Literature-anchored findings (GeneRIF, showing 5)

• MEI1 may play a role in meiosis during spermatogenesis, especially in European Americans. (PMID:16683055)
• we report on a homozygous missense mutation in the gene coding for meiotic double-stranded break formation protein 1 observed in two brothers with non-obstructive azoospermia and meiotic arrest. A fertile brother was heterozygous for the mutation. All the queried databases predicted that this mutation is damaging, and it has previously been reported that Mei1 knock-out is associated with meiotic arrest in a murine model. (PMID:29659827)
• Novel biallelic mutations in MEI1: expanding the phenotypic spectrum to human embryonic arrest and recurrent implantation failure. (PMID:34037756)
• Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia. (PMID:36759719)
• Novel MEI1 mutations cause chromosomal and DNA methylation abnormalities leading to embryonic arrest and implantation failure. (PMID:38416203)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mei1	ENSMUSG00000068117
rattus_norvegicus	Mei1	ENSRNOG00000007003

Paralogs (2): BCL2L11 (ENSG00000153094), SCIMP (ENSG00000161929)

Protein

Protein identifiers

Meiosis inhibitor protein 1 — Q5TIA1 (reviewed: Q5TIA1)

Alternative names: Meiosis defective protein 1

All UniProt accessions (3): Q5TIA1, F5GZT0, H0Y787

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal meiotic chromosome synapsis. May be involved in the formation of meiotic double-strand breaks (DSBs) in spermatocytes.

Tissue specificity. Expressed predominantly in testis. Weakly expressed in spleen and thymus. Expressed in the ovaries, Fallopian tubes and uterus.

Disease relevance. Hydatidiform mole, recurrent, 3 (HYDM3) [MIM:618431] A disorder characterized by excessive trophoblast development that produces a growing mass of tissue inside the uterus at the beginning of a pregnancy. It leads to abnormal pregnancies with no embryo, and cystic degeneration of the chorionic villi. The disease is caused by variants affecting the gene represented in this entry. Susceptibility to azoospermia may be associated with MEI1 variations.

Isoforms (7)

UniProt ID	Names	Canonical?
Q5TIA1-1	1	yes
Q5TIA1-2	2, Long
Q5TIA1-3	3, Short
Q5TIA1-4	4
Q5TIA1-5	5
Q5TIA1-6	6
Q5TIA1-7	7

RefSeq proteins (1): NP_689726* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR052133	Immune_Signaling-Apoptosis_Reg	Family

UniProt features (18 total): splice variant 9, sequence variant 7, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TIA1-F1	84.09	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 51 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, ZHAN_MULTIPLE_MYELOMA_PR_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_ORGANELLE_FISSION, SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_MEIOTIC_CELL_CYCLE, chr22q13, GOBP_CELL_CYCLE_PROCESS, MATZUK_MEIOTIC_AND_DNA_REPAIR, MATZUK_SPERMATOCYTE, GOBP_MEIOSIS_I_CELL_CYCLE_PROCESS, ID1_TARGET_GENES, ZNF664_TARGET_GENES, MIR7159_5P

GO Biological Process (2): meiosis I (GO:0007127), meiotic cell cycle (GO:0051321)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
meiotic nuclear division	2
meiotic telophase I	1
meiosis I cell cycle process	1
cell cycle	1
sexual reproduction	1
reproductive process	1

Protein interactions and networks

STRING

746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEI1	REC114	Q7Z4M0	906
MEI1	SPO11	Q9Y5K1	881
MEI1	IHO1	Q8IYA8	805
MEI1	MEI4	A8MW99	793
MEI1	ANKRD31	Q8N7Z5	777
MEI1	MORC1	Q86VD1	768
MEI1	HORMAD1	Q86X24	723
MEI1	SYCE1	Q8N0S2	717
MEI1	TOP6BL	Q8N6T0	712
MEI1	NAE1	Q13564	677
MEI1	SYCP1	Q15431	675
MEI1	UBE2M	P61081	673
MEI1	CTSA	P10619	649
MEI1	CUL3	Q13618	609
MEI1	SYCP3	Q8IZU3	605

IntAct

4 interactions, top by confidence:

A	B	Type	Score
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
MEI1	PMPCB	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): MEI1 (Affinity Capture-RNA), PMPCB (Affinity Capture-MS), TK1 (Affinity Capture-MS), PMPCA (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), GPAT2 (Affinity Capture-MS), TRABD (Affinity Capture-MS), MEI1 (Affinity Capture-MS), MEI1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM23, A4D1B5, A6NDU8, A8C754, A8MW99, A8Y5U1, O43149, O55036, O75901, O88480, P42695, P54274, P93820, Q14AT2, Q3U1D0, Q3UPC7, Q3URV1, Q4R7B1, Q5SSH7, Q5TIA1, Q5ZLS8, Q63517, Q642P2, Q68Y81, Q6P2C0, Q6TNU3, Q6ZQK0, Q86VV8, Q8AYS7, Q8BR90, Q8BRM6, Q8C6S9, Q8K1K4, Q8K2A7, Q8NG48, Q8R4Y8, Q8TDY2, Q8TEL6, Q8W4P9, Q91VB4

Diamond homologs: Q5TIA1, Q9D4I2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	7
Uncertain significance	141
Likely benign	34
Benign	19

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
2079114	NM_152513.4(MEI1):c.1000_1003del (p.Ser334fs)	Pathogenic
627577	NM_152513.4(MEI1):c.1196+1G>A	Pathogenic
627578	NM_152513.4(MEI1):c.2206del (p.Val736fs)	Pathogenic
2068049	NM_152513.4(MEI1):c.1538+1G>A	Likely pathogenic
2137679	NM_152513.4(MEI1):c.3170-1G>C	Likely pathogenic
2157329	NM_152513.4(MEI1):c.1097-1G>C	Likely pathogenic
2442306	NM_152513.4(MEI1):c.3772G>T (p.Asp1258Tyr)	Likely pathogenic
4686563	NM_152513.4(MEI1):c.2339del (p.Pro780fs)	Likely pathogenic
4849214	NM_152513.4(MEI1):c.445C>T (p.Arg149Ter)	Likely pathogenic
627576	NM_152513.4(MEI1):c.3452G>A (p.Trp1151Ter)	Likely pathogenic

SpliceAI

6049 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41703329:A:G	acceptor_gain	1.0000
22:41705495:T:TA	acceptor_gain	1.0000
22:41716040:GCT:G	acceptor_gain	1.0000
22:41723940:TAGGT:T	acceptor_loss	1.0000
22:41723941:AGG:A	acceptor_loss	1.0000
22:41724069:AAAAG:A	donor_loss	1.0000
22:41724070:AAAGG:A	donor_loss	1.0000
22:41724071:AAGGT:A	donor_loss	1.0000
22:41724073:GGTAG:G	donor_loss	1.0000
22:41724074:G:A	donor_loss	1.0000
22:41724075:T:G	donor_loss	1.0000
22:41732239:T:TA	acceptor_gain	1.0000
22:41753947:A:G	acceptor_gain	1.0000
22:41758363:A:AG	acceptor_gain	1.0000
22:41758364:G:GA	acceptor_gain	1.0000
22:41758364:G:GC	acceptor_loss	1.0000
22:41758364:GA:G	acceptor_gain	1.0000
22:41758364:GAA:G	acceptor_gain	1.0000
22:41758364:GAAC:G	acceptor_gain	1.0000
22:41758364:GAACT:G	acceptor_gain	1.0000
22:41758529:GACAG:G	donor_gain	1.0000
22:41758533:GGT:G	donor_loss	1.0000
22:41758534:G:A	donor_loss	1.0000
22:41758535:T:G	donor_loss	1.0000
22:41776264:GGAG:G	donor_gain	1.0000
22:41776265:G:GT	donor_gain	1.0000
22:41793958:G:GT	donor_gain	1.0000
22:41699590:G:GT	donor_gain	0.9900
22:41699954:G:GT	donor_gain	0.9900
22:41699995:G:T	donor_gain	0.9900

AlphaMissense

8277 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41729701:A:C	S301R	0.997
22:41729703:T:A	S301R	0.997
22:41729703:T:G	S301R	0.997
22:41724070:A:C	K287N	0.991
22:41724070:A:T	K287N	0.991
22:41724069:A:T	K287I	0.989
22:41730523:T:C	F328L	0.989
22:41730525:C:A	F328L	0.989
22:41730525:C:G	F328L	0.989
22:41730637:G:T	G366W	0.988
22:41794394:T:A	W1151R	0.987
22:41794394:T:C	W1151R	0.987
22:41729726:T:C	L309P	0.985
22:41730613:T:C	F358L	0.984
22:41730615:T:A	F358L	0.984
22:41730615:T:G	F358L	0.984
22:41732245:G:A	G366E	0.983
22:41724066:T:C	L286P	0.981
22:41729710:T:C	C304R	0.981
22:41730637:G:A	G366R	0.980
22:41730637:G:C	G366R	0.980
22:41745931:T:C	F529L	0.980
22:41745933:C:A	F529L	0.980
22:41745933:C:G	F529L	0.980
22:41732245:G:T	G366V	0.979
22:41732338:T:C	L397P	0.978
22:41730611:T:C	F357S	0.977
22:41781795:T:A	W1013R	0.977
22:41781795:T:C	W1013R	0.977
22:41699641:T:A	W35R	0.976

dbSNP variants (sampled 300 via entrez): RS1000037573 (22:41783472 A>G), RS1000044144 (22:41704979 G>T), RS1000057036 (22:41783931 C>T), RS1000108267 (22:41712515 G>A), RS1000138613 (22:41769682 G>A), RS1000270736 (22:41795036 T>C), RS1000297303 (22:41739165 G>A), RS1000301101 (22:41766350 T>C,G), RS1000326774 (22:41783720 G>A,T), RS1000361492 (22:41734318 C>T), RS1000366521 (22:41778018 C>T), RS1000378854 (22:41726935 A>G), RS1000394697 (22:41765625 A>G), RS1000414033 (22:41734105 G>A), RS1000415313 (22:41705192 T>C)

Disease associations

OMIM: gene MIM:608797 | disease phenotypes: MIM:618431

GenCC curated gene-disease

Disease	Classification	Inheritance
hydatidiform mole, recurrent, 3	Strong	Autosomal recessive
complete hydatidiform mole	Supportive	Autosomal recessive

Mondo (2): hydatidiform mole, recurrent, 3 (MONDO:0032746), complete hydatidiform mole (MONDO:0016785)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0008222	Female infertility
HP:0011462	Young adult onset
HP:0032192	Hydatidiform mole

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005232_52	Neuroticism	3.000000e-18
GCST006291_18	Spherical equivalent or myopia (age of diagnosis)	4.000000e-08
GCST007269_281	Pulse pressure	5.000000e-10
GCST010002_83	Refractive error	2.000000e-27
GCST010143_2	Meat-related diet	4.000000e-08
GCST90002393_592	Monocyte count	8.000000e-11
GCST90002394_209	Monocyte percentage of white cells	5.000000e-15

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004847	age at onset
EFO:0005763	pulse pressure measurement
EFO:0008111	diet measurement
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Diuron	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00521118	PHASE2	COMPLETED	Second Curettage in Treating Patients With Persistent Non-metastatic Gestational Trophoblastic Tumors