GMNC

Summary

GMNC (geminin coiled-coil domain containing, HGNC:40049) is a protein-coding gene on chromosome 3q28, encoding Geminin coiled-coil domain-containing protein 1 (A6NCL1). Regulator of DNA replication.

Predicted to enable chromatin binding activity. Predicted to be involved in negative regulation of cell cycle and regulation of DNA-templated DNA replication initiation. Predicted to act upstream of or within several processes, including cerebrospinal fluid circulation; multi-ciliated epithelial cell differentiation; and seminiferous tubule development. Predicted to be located in extracellular region. Predicted to be active in nucleus.

Source: NCBI Gene 647309 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001146686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40049
Approved symbol	GMNC
Name	geminin coiled-coil domain containing
Location	3q28
Locus type	gene with protein product
Status	Approved
Aliases	GEMC1
Ensembl gene	ENSG00000205835
Ensembl biotype	protein_coding
OMIM	614448
Entrez	647309

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 1 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000442080, ENST00000456552, ENST00000479491, ENST00000495042

RefSeq mRNA: 1 — MANE Select: NM_001146686 NM_001146686

CCDS: CCDS54697

Canonical transcript exons

ENST00000442080 — 5 exons

Exon	Start	End
ENSE00001490706	190860684	190860858
ENSE00001795538	190852737	190855915
ENSE00002503205	190862613	190862694
ENSE00003579282	190857783	190857899
ENSE00003663911	190858928	190859016

Expression profiles

Bgee: expression breadth broad, 77 present calls, max score 81.41.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3048 / max 56.0261, expressed in 127 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46094	0.1744	61
46095	0.0988	45
46096	0.0316	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	81.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.24	gold quality
right lobe of liver	UBERON:0001114	68.16	gold quality
left uterine tube	UBERON:0001303	65.51	gold quality
fallopian tube	UBERON:0003889	61.50	gold quality
liver	UBERON:0002107	59.84	gold quality
adult mammalian kidney	UBERON:0000082	56.73	gold quality
smooth muscle tissue	UBERON:0001135	55.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.58	gold quality
right testis	UBERON:0004534	53.49	gold quality
endometrium	UBERON:0001295	53.47	gold quality
left testis	UBERON:0004533	53.29	gold quality
testis	UBERON:0000473	53.07	gold quality
kidney	UBERON:0002113	52.00	gold quality
body of pancreas	UBERON:0001150	49.26	gold quality
cerebellar vermis	UBERON:0004720	48.32	gold quality
cortex of kidney	UBERON:0001225	48.30	gold quality
hypothalamus	UBERON:0001898	47.71	gold quality
corpus callosum	UBERON:0002336	47.67	gold quality
caput epididymis	UBERON:0004358	47.55	gold quality
ventricular zone	UBERON:0003053	47.42	silver quality
pancreas	UBERON:0001264	47.36	gold quality
heart left ventricle	UBERON:0002084	47.36	gold quality
cardiac ventricle	UBERON:0002082	47.11	gold quality
prefrontal cortex	UBERON:0000451	46.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	45.59	gold quality
uterus	UBERON:0000995	45.09	gold quality
oviduct epithelium	UBERON:0004804	44.97	gold quality
metanephros cortex	UBERON:0010533	44.81	gold quality
islet of Langerhans	UBERON:0000006	44.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

175 targeting GMNC, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 2)

• The crystal structure of a GemC1 coiled-coil domain variant engineered for better solubility was determined to 2.2 A resolution. (PMID:26527144)
• Transcriptional regulation of multiciliated cell differentiation. (PMID:32362381)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gmnc	ENSDARG00000068719
mus_musculus	Gmnc	ENSMUSG00000068428
rattus_norvegicus	Gmnc	ENSRNOG00000038505
drosophila_melanogaster	geminin	FBGN0033081

Paralogs (2): GMNN (ENSG00000112312), MCIDAS (ENSG00000234602)

Protein

Protein identifiers

Geminin coiled-coil domain-containing protein 1 — A6NCL1 (reviewed: A6NCL1)

All UniProt accessions (2): A6NCL1, G5E9I9

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of DNA replication. Promotes initiation of chromosomal DNA replication by mediating TOPBP1- and CDK2-dependent recruitment of CDC45L onto replication origins.

Subcellular location. Nucleus.

Post-translational modifications. Highly phosphorylated by CDK2; stimulates initiation of DNA replication.

Similarity. Belongs to the GEMC1 family.

RefSeq proteins (1): NP_001140158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR059237	GemC1_CC	Domain

UniProt features (4 total): chain 1, region of interest 1, coiled-coil region 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5C9N	X-RAY DIFFRACTION	2.2
9HIU	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NCL1-F1	60.10	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_SINGLE_FERTILIZATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_GROWTH, GOBP_MALE_GAMETE_GENERATION, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_MULTICELLULAR_ORGANISM_GROWTH, GOBP_ORGANELLE_ASSEMBLY, GOBP_COLUMNAR_CUBOIDAL_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (11): DNA replication (GO:0006260), spermatogenesis (GO:0007283), single fertilization (GO:0007338), regulation of DNA-templated DNA replication initiation (GO:0030174), multicellular organism growth (GO:0035264), negative regulation of cell cycle (GO:0045786), positive regulation of transcription by RNA polymerase II (GO:0045944), cilium assembly (GO:0060271), seminiferous tubule development (GO:0072520), cerebrospinal fluid circulation (GO:0090660), multi-ciliated epithelial cell differentiation (GO:1903251)

GO Molecular Function (3): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
binding	2
DNA metabolic process	1
DNA biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
fertilization	1
DNA replication initiation	1
regulation of DNA-templated DNA replication	1
multicellular organismal process	1
developmental growth	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
male gonad development	1
tube development	1
reproductive structure development	1
epithelial cilium movement involved in extracellular fluid movement	1
nervous system process	1
columnar/cuboidal epithelial cell differentiation	1
transcription coregulator activity	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GMNC	MCIDAS	D6RGH6	902
GMNC	E2F5	Q15329	899
GMNC	TOPBP1	Q92547	750
GMNC	E2F4	Q16254	712
GMNC	FOXJ1	Q92949	687
GMNC	OSTN	P61366	683
GMNC	CCNO	P22674	666
GMNC	RFX2	P48378	644
GMNC	TICRR	Q7Z2Z1	626
GMNC	DEUP1	Q05D60	622
GMNC	RFX4	Q33E94	520
GMNC	CDK2	P24941	504
GMNC	MAB21L3	Q8N8X9	493
GMNC	CDC45	O75419	493
GMNC	RECQL4	O94761	475

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GMNC	CCNE1	psi-mi:“MI:0915”(physical association)	0.560
CCNE1	GMNC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): GMNC (Synthetic Lethality), GMNC (Two-hybrid)

ESM2 similar proteins: A0P8Z5, A6NCL1, A8E4V2, B5DF41, D3YN49, D3ZDX9, D6RGH6, F1QN48, F1SLM8, F7BHS0, G3N1S4, O15079, P12841, P20389, P24793, P97432, Q08B36, Q14140, Q14596, Q14DQ1, Q1LWL8, Q3SYW5, Q3U827, Q3UKU1, Q3URY2, Q3UZ45, Q4KMA0, Q4R3X1, Q501R9, Q5R8C5, Q5RC94, Q5RD40, Q64210, Q6P2K3, Q6ZNC4, Q80U23, Q80YE2, Q8NFW9, Q8R0W1, Q96A56

Diamond homologs: A6NCL1, D3YN49, D6RGH6, F1SLM8, F7BHS0, Q08B36, Q3URY2, D3ZDX9, G3N1S4, O88513, Q3UZ45

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

550 predictions. Top by Δscore:

Variant	Effect	Δscore
3:190857779:ATAC:A	donor_loss	1.0000
3:190857895:TGCAG:T	acceptor_gain	1.0000
3:190857896:GCAG:G	acceptor_gain	1.0000
3:190857897:CAG:C	acceptor_gain	1.0000
3:190857897:CAGC:C	acceptor_gain	1.0000
3:190857898:AG:A	acceptor_gain	1.0000
3:190857899:GCTA:G	acceptor_loss	1.0000
3:190857900:C:CC	acceptor_gain	1.0000
3:190858923:CATA:C	donor_loss	1.0000
3:190858924:ATAC:A	donor_loss	1.0000
3:190858925:TA:T	donor_loss	1.0000
3:190858926:ACC:A	donor_loss	1.0000
3:190858927:C:G	donor_loss	1.0000
3:190858927:CCTG:C	donor_gain	1.0000
3:190859012:TGATT:T	acceptor_gain	1.0000
3:190859013:GATT:G	acceptor_gain	1.0000
3:190859014:ATT:A	acceptor_gain	1.0000
3:190859014:ATTC:A	acceptor_loss	1.0000
3:190859015:TT:T	acceptor_gain	1.0000
3:190859015:TTCT:T	acceptor_loss	1.0000
3:190859016:TC:T	acceptor_loss	1.0000
3:190859017:C:CC	acceptor_gain	1.0000
3:190859017:CT:C	acceptor_loss	1.0000
3:190859018:T:C	acceptor_loss	1.0000
3:190859019:G:C	acceptor_gain	1.0000
3:190859019:G:GC	acceptor_gain	1.0000
3:190857781:A:AC	donor_gain	0.9900
3:190857782:C:CC	donor_gain	0.9900
3:190857898:AGCT:A	acceptor_gain	0.9900
3:190857899:GCT:G	acceptor_gain	0.9900

AlphaMissense

2194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:190855315:A:G	W329R	0.999
3:190855315:A:T	W329R	0.999
3:190855313:C:A	W329C	0.998
3:190855313:C:G	W329C	0.998
3:190855320:A:G	F327S	0.998
3:190855716:A:G	L195S	0.998
3:190857865:A:G	L101P	0.998
3:190855352:A:C	F316L	0.997
3:190855352:A:T	F316L	0.997
3:190855354:A:G	F316L	0.997
3:190857835:A:G	L111P	0.997
3:190857898:A:G	L90P	0.997
3:190855353:A:G	F316S	0.996
3:190855363:C:G	G313R	0.996
3:190855363:C:T	G313R	0.996
3:190855370:G:C	F310L	0.996
3:190855370:G:T	F310L	0.996
3:190855372:A:G	F310L	0.996
3:190855415:A:C	F295L	0.996
3:190855415:A:T	F295L	0.996
3:190855417:A:G	F295L	0.996
3:190855314:C:G	W329S	0.995
3:190855327:A:G	W325R	0.995
3:190855327:A:T	W325R	0.995
3:190855356:G:T	A315D	0.995
3:190855362:C:T	G313E	0.995
3:190855371:A:G	F310S	0.993
3:190855353:A:C	F316C	0.992
3:190857856:A:G	L104S	0.992
3:190857886:A:G	L94P	0.992

dbSNP variants (sampled 300 via entrez): RS1000136479 (3:190847902 G>A), RS1000153109 (3:190854887 T>G), RS1000186395 (3:190859370 C>T), RS1000282746 (3:190847702 C>G), RS1000476606 (3:190843127 T>A,G), RS1000493906 (3:190853376 T>C,G), RS1000656175 (3:190863685 T>C), RS1000725753 (3:190849080 G>A), RS1001049529 (3:190859432 A>T), RS1001094300 (3:190846709 C>A,G), RS1001109788 (3:190853699 C>A), RS1001486659 (3:190860561 C>T), RS1001527723 (3:190862820 C>A), RS1001623149 (3:190856589 T>C,G), RS1001780031 (3:190856415 T>A,G)

Disease associations

OMIM: gene MIM:614448 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001951_1	Alzheimer’s disease biomarkers	5.000000e-09
GCST004070_11	Cerebrospinal P-tau181p levels	6.000000e-10
GCST004071_3	Cerebrospinal T-tau levels	3.000000e-11
GCST010699_100	Brain morphology (min-P)	1.000000e-11
GCST010701_87	Cortical surface area (MOSTest)	1.000000e-08
GCST010702_32	Subcortical volume (MOSTest)	9.000000e-11
GCST010703_90	Brain morphology (MOSTest)	1.000000e-72
GCST012008_3	Lateral thalamic nuclei volume	3.000000e-10
GCST012010_4	Medial thalamic nuclei volume	8.000000e-15
GCST012011_1	Ventral thalamic nuclei volume	1.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0004763	p-tau measurement
EFO:0004346	neuroimaging measurement
EFO:0006935	thalamus volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-palmitoylglycerol	increases expression	1
Benzo(a)pyrene	affects methylation	1
Malathion	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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