GMCL1

Summary

GMCL1 (germ cell-less 1, spermatogenesis associated, HGNC:23843) is a protein-coding gene on chromosome 2p13.3, encoding Germ cell-less protein-like 1 (Q96IK5). Possible function in spermatogenesis.

This gene encodes a nuclear envelope protein that appears to be involved in spermatogenesis, either directly or by influencing genes that play a more direct role in the process. This multi-exon locus is the homolog of the mouse and drosophila germ cell-less gene but the human genome also contains a single-exon locus on chromosome 5 that contains an open reading frame capable of encoding a highly-related protein.

Source: NCBI Gene 64395 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_178439

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23843
Approved symbol	GMCL1
Name	germ cell-less 1, spermatogenesis associated
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13057, BTBD13, GCL1, SPATA29
Ensembl gene	ENSG00000087338
Ensembl biotype	protein_coding
OMIM	618627
Entrez	64395

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000282570, ENST00000468386, ENST00000471404, ENST00000495047, ENST00000885038, ENST00000885039, ENST00000885040, ENST00000885041, ENST00000916919, ENST00000947258

RefSeq mRNA: 1 — MANE Select: NM_178439 NM_178439

CCDS: CCDS1895

Canonical transcript exons

ENST00000282570 — 14 exons

Exon	Start	End
ENSE00000759462	69854823	69854960
ENSE00000759465	69864900	69864975
ENSE00000846463	69840942	69841039
ENSE00000846464	69843149	69843261
ENSE00000846469	69861278	69861347
ENSE00000846471	69869719	69869864
ENSE00001006481	69878909	69881384
ENSE00001847160	69829660	69830152
ENSE00003462378	69844131	69844196
ENSE00003505301	69847543	69847627
ENSE00003516750	69871745	69871832
ENSE00003516752	69849652	69849742
ENSE00003605490	69839457	69839553
ENSE00003687792	69837547	69837670

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 91.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8281 / max 210.8419, expressed in 1778 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20773	13.5120	1775
20774	0.2135	80
20775	0.1027	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	91.68	gold quality
oocyte	CL:0000023	91.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.80	gold quality
calcaneal tendon	UBERON:0003701	85.42	gold quality
adult organism	UBERON:0007023	85.39	gold quality
rectum	UBERON:0001052	84.99	gold quality
monocyte	CL:0000576	84.81	gold quality
islet of Langerhans	UBERON:0000006	84.74	gold quality
leukocyte	CL:0000738	84.72	gold quality
mononuclear cell	CL:0000842	84.66	gold quality
duodenum	UBERON:0002114	84.65	gold quality
choroid plexus epithelium	UBERON:0003911	84.13	gold quality
jejunal mucosa	UBERON:0000399	83.88	gold quality
ganglionic eminence	UBERON:0004023	83.40	gold quality
bone marrow	UBERON:0002371	83.39	gold quality
testis	UBERON:0000473	83.30	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.87	gold quality
popliteal artery	UBERON:0002250	82.85	gold quality
tibial artery	UBERON:0007610	82.85	gold quality
ventricular zone	UBERON:0003053	82.82	gold quality
left testis	UBERON:0004533	82.81	gold quality
right testis	UBERON:0004534	82.56	gold quality
artery	UBERON:0001637	82.38	gold quality
bone marrow cell	CL:0002092	82.15	gold quality
pancreas	UBERON:0001264	82.10	gold quality
body of pancreas	UBERON:0001150	81.89	gold quality
aorta	UBERON:0000947	81.50	gold quality
bronchial epithelial cell	CL:0002328	81.48	gold quality
gall bladder	UBERON:0002110	81.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

170 targeting GMCL1, 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-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
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-4267	99.96	66.53	2368
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6744-5P	99.93	66.82	748

Literature-anchored findings (GeneRIF, showing 5)

• GCL binds directly to emerin, and the emerin-repressor complexes might be regulated by barrier to autointegration factor (PMID:12493765)
• mGCL-1 is a factor modulating MDM2-p53 axis by enhanced degradation of MDM2 (PMID:12927808)
• Germ cell-less protein is not essential for the chromosomal events of meiosis but might be involved in later aspects of spermatogenesis. (PMID:12954656)
• Dual association of GAGE family members with GCL at the nuclear envelope inner membrane in cells, and with dsDNA in vitro, implicate GAGE proteins in chromatin regulation in germ cells and cancer cells. (PMID:23029259)
• Mouse GMCL1 interacts with the DP component of the E2F transcription factor. (PMID:9878064)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gmcl1	ENSDARG00000020948
mus_musculus	Gmcl1	ENSMUSG00000001157
rattus_norvegicus	Gmcl1	ENSRNOG00000017838
drosophila_melanogaster	gcl	FBGN0005695
caenorhabditis_elegans		WBGENE00013382

Paralogs (3): BTBD16 (ENSG00000138152), C10orf120 (ENSG00000183559), GMCL2 (ENSG00000244234)

Protein

Protein identifiers

Germ cell-less protein-like 1 — Q96IK5 (reviewed: Q96IK5)

Alternative names: Spermatogenesis-associated protein 29

All UniProt accessions (2): Q96IK5, Q53SE7

UniProt curated annotations — full annotation on UniProt →

Function. Possible function in spermatogenesis. Enhances the degradation of MDM2 and increases the amount of p53 probably by modulating the nucleocytoplasmic transport.

Subunit / interactions. Interacts with TMPO-beta, TSG101 and TFDP2. Interacts with EMD.

Subcellular location. Nucleus matrix.

RefSeq proteins (1): NP_848526* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR043380	Gcl-like	Family

Pfam: PF00651, PF07707

UniProt features (15 total): sequence conflict 5, region of interest 2, short sequence motif 2, compositionally biased region 2, modified residue 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IK5-F1	84.82	0.74

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): 66, 68

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): PEREZ_TP63_TARGETS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_MALE_GAMETE_GENERATION, PATIL_LIVER_CANCER, MODULE_171, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, PEREZ_TP53_AND_TP63_TARGETS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, LIU_CMYB_TARGETS_UP, LIU_VMYB_TARGETS_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, MATZUK_SPERMATOZOA, STEIN_ESRRA_TARGETS_UP, chr2p13

GO Biological Process (3): germ cell development (GO:0007281), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nuclear matrix (GO:0016363)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
male gamete generation	1
cellular developmental process	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GMCL1	USHBP1	Q8N6Y0	510
GMCL1	SPIN4	Q56A73	506
GMCL1	ZBTB25	P24278	407
GMCL1	ADAM20	O43506	402
GMCL1	NTMT2	Q5VVY1	388
GMCL1	FAM13B	Q9NYF5	387
GMCL1	FAM98C	Q17RN3	372
GMCL1	SPATA6	Q9NWH7	362
GMCL1	PGAM1	P18669	353
GMCL1	PGAM4	Q8N0Y7	353
GMCL1	PRR14	Q9BWN1	352
GMCL1	KIF4B	Q2VIQ3	340
GMCL1	SPATA1	Q5VX52	338
GMCL1	STYXL1	Q9Y6J8	328
GMCL1	H0YHX9	H0YHX9	324

IntAct

367 interactions, top by confidence:

A	B	Type	Score
GMCL1	FAM167A	psi-mi:“MI:0915”(physical association)	0.800
GMCL1	XAGE3	psi-mi:“MI:0915”(physical association)	0.800
XAGE3	GMCL1	psi-mi:“MI:0915”(physical association)	0.800
FAM167A	GMCL1	psi-mi:“MI:0915”(physical association)	0.800
MID1	GMCL1	psi-mi:“MI:0915”(physical association)	0.780
CUL3	GMCL1	psi-mi:“MI:0915”(physical association)	0.740
GMCL1	GMCL1	psi-mi:“MI:0915”(physical association)	0.720
PAX4	GMCL1	psi-mi:“MI:0915”(physical association)	0.720
BYSL	GMCL1	psi-mi:“MI:0915”(physical association)	0.700
KAT5	GMCL1	psi-mi:“MI:0915”(physical association)	0.700
QRICH1	GMCL1	psi-mi:“MI:0915”(physical association)	0.700
GMCL1	BYSL	psi-mi:“MI:0915”(physical association)	0.700
CCKBR	PRKAG1	psi-mi:“MI:0914”(association)	0.640
GMCL1	ADY3	psi-mi:“MI:0915”(physical association)	0.610
GMCL1		psi-mi:“MI:0915”(physical association)	0.560
GMCL1	MAS1	psi-mi:“MI:0915”(physical association)	0.560
SUI2	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
REC107	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
GMCL1	ASP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (279): GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid), GMCL1 (Two-hybrid)

ESM2 similar proteins: A4FUF0, A5HK05, B0K012, O43324, O43929, O75431, O94955, O95453, P20135, P42694, P47802, P69341, P70102, P78417, Q2L969, Q3U2J5, Q3UFS0, Q49A26, Q4R8V9, Q562D5, Q5R6Z7, Q5R7T2, Q5RC51, Q5RDU9, Q5RKH0, Q5ZIA0, Q5ZLS2, Q5ZLS7, Q6AXV9, Q6DC64, Q6DFV5, Q6GR37, Q6NYU2, Q7SXV1, Q7Z624, Q8IX04, Q8K2D3, Q8K2Q2, Q8R5L3, Q8VE33

Diamond homologs: Q01820, Q8NEA9, Q920G9, Q96IK5, Q99N64, Q6NRS1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1968 predictions. Top by Δscore:

Variant	Effect	Δscore
2:69830151:AGG:A	donor_loss	1.0000
2:69830152:GGTA:G	donor_loss	1.0000
2:69830153:G:C	donor_loss	1.0000
2:69837666:GTCAA:G	donor_gain	1.0000
2:69837667:TCAAG:T	donor_loss	1.0000
2:69837668:CAAG:C	donor_loss	1.0000
2:69837669:AAGTA:A	donor_loss	1.0000
2:69837670:AG:A	donor_loss	1.0000
2:69837671:G:C	donor_loss	1.0000
2:69837671:G:GG	donor_gain	1.0000
2:69837672:TAA:T	donor_loss	1.0000
2:69839454:A:AG	acceptor_gain	1.0000
2:69839455:A:G	acceptor_gain	1.0000
2:69839455:AGTCT:A	acceptor_gain	1.0000
2:69839456:G:GA	acceptor_gain	1.0000
2:69839456:GT:G	acceptor_gain	1.0000
2:69839456:GTCT:G	acceptor_gain	1.0000
2:69839456:GTCTG:G	acceptor_gain	1.0000
2:69839472:A:AG	acceptor_gain	1.0000
2:69839473:G:GG	acceptor_gain	1.0000
2:69839549:AGAAG:A	donor_loss	1.0000
2:69839550:GAAGG:G	donor_loss	1.0000
2:69839551:AAGGT:A	donor_loss	1.0000
2:69839552:AGGTA:A	donor_loss	1.0000
2:69839553:GG:G	donor_loss	1.0000
2:69839554:G:GA	donor_loss	1.0000
2:69839555:T:G	donor_loss	1.0000
2:69840924:T:G	acceptor_gain	1.0000
2:69840929:ACCTT:A	acceptor_gain	1.0000
2:69840933:T:A	acceptor_gain	1.0000

AlphaMissense

3407 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:69864950:G:A	G398D	1.000
2:69869725:T:A	W409R	1.000
2:69869725:T:C	W409R	1.000
2:69869731:T:A	W411R	1.000
2:69869731:T:C	W411R	1.000
2:69869733:G:C	W411C	1.000
2:69869733:G:T	W411C	1.000
2:69869797:C:A	R433S	1.000
2:69837591:T:C	F102S	0.999
2:69837650:C:G	H122D	0.999
2:69849652:T:A	W282R	0.999
2:69849652:T:C	W282R	0.999
2:69861307:T:A	W368R	0.999
2:69861307:T:C	W368R	0.999
2:69864944:G:C	R396T	0.999
2:69864944:G:T	R396M	0.999
2:69864945:G:C	R396S	0.999
2:69864945:G:T	R396S	0.999
2:69864954:A:C	R399S	0.999
2:69864954:A:T	R399S	0.999
2:69869727:G:C	W409C	0.999
2:69869727:G:T	W409C	0.999
2:69869728:C:A	R410S	0.999
2:69869729:G:C	R410P	0.999
2:69869732:G:C	W411S	0.999
2:69869740:T:C	F414L	0.999
2:69869742:T:A	F414L	0.999
2:69869742:T:G	F414L	0.999
2:69869756:A:C	D419A	0.999
2:69869756:A:G	D419G	0.999

dbSNP variants (sampled 300 via entrez): RS1000032898 (2:69858687 C>A,T), RS1000040630 (2:69877040 A>C), RS1000067923 (2:69833439 A>C), RS1000129886 (2:69856451 G>T), RS1000222953 (2:69840115 G>A), RS1000223643 (2:69833344 G>A), RS1000283148 (2:69830281 G>A), RS1000307422 (2:69849320 C>G), RS1000356699 (2:69843251 G>A), RS1000396494 (2:69828132 A>G,T), RS1000396764 (2:69870831 A>G,T), RS1000432472 (2:69877770 T>TA), RS1000530803 (2:69831272 A>G), RS1000565389 (2:69838459 G>C), RS1000595854 (2:69831779 T>C)

Disease associations

OMIM: gene MIM:618627 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003208_10	Colorectal or endometrial cancer	6.000000e-06
GCST004297_2	Atrial fibrillation	1.000000e-10
GCST006061_30	Atrial fibrillation	1.000000e-17
GCST006414_66	Atrial fibrillation	1.000000e-16
GCST009200_21	Whole brain grey matter density	2.000000e-06
GCST90002404_20	Red cell distribution width	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004230	endometrial neoplasm
EFO:0010306	Grey matter density measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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