GCM1

Summary

GCM1 (GCM transcription factor 1, HGNC:4197) is a protein-coding gene on chromosome 6p12.1, encoding Chorion-specific transcription factor GCMa (Q9NP62). Transcription factor involved in the control of expression of placental growth factor (PGF) and other placenta-specific genes.

This gene encodes a DNA-binding protein with a gcm-motif (glial cell missing motif). The encoded protein is a homolog of the Drosophila glial cells missing gene (gcm). This protein binds to the GCM-motif (A/G)CCCGCAT, a novel sequence among known targets of DNA-binding proteins. The N-terminal DNA-binding domain confers the unique DNA-binding activity of this protein.

Source: NCBI Gene 8521 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 62 total
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_003643

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4197
Approved symbol	GCM1
Name	GCM transcription factor 1
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	hGCMa
Ensembl gene	ENSG00000137270
Ensembl biotype	protein_coding
OMIM	603715
Entrez	8521

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000259803

RefSeq mRNA: 1 — MANE Select: NM_003643 NM_003643

CCDS: CCDS4950

Canonical transcript exons

ENST00000259803 — 6 exons

Exon	Start	End
ENSE00000929857	53134072	53134324
ENSE00000929858	53132007	53132119
ENSE00000929859	53130803	53130931
ENSE00001346598	53148754	53148841
ENSE00001412733	53126961	53128946
ENSE00001420113	53145558	53145768

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 92.03.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5802 / max 221.7782, expressed in 20 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73993	0.5167	18
73992	0.0635	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	92.03	gold quality
decidua	UBERON:0002450	81.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.33	gold quality
sperm	CL:0000019	56.86	silver quality
blood	UBERON:0000178	55.84	gold quality
nephron tubule	UBERON:0001231	53.14	gold quality
pancreatic ductal cell	CL:0002079	52.62	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
adult mammalian kidney	UBERON:0000082	51.77	gold quality
islet of Langerhans	UBERON:0000006	51.32	gold quality
middle temporal gyrus	UBERON:0002771	50.51	gold quality
buccal mucosa cell	CL:0002336	50.44	gold quality
kidney epithelium	UBERON:0004819	50.28	silver quality
leukocyte	CL:0000738	49.93	silver quality
epithelial cell of pancreas	CL:0000083	49.92	gold quality
metanephros	UBERON:0000081	49.74	silver quality
mononuclear cell	CL:0000842	49.72	gold quality
kidney	UBERON:0002113	49.71	gold quality
monocyte	CL:0000576	49.54	gold quality
metanephric glomerulus	UBERON:0004736	49.32	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
quadriceps femoris	UBERON:0001377	49.13	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
thymus	UBERON:0002370	48.90	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
granulocyte	CL:0000094	48.86	silver quality
type B pancreatic cell	CL:0000169	48.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	565.27
E-ANND-3	yes	4.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
CDH17
CREBBP
CYP19A1	Unknown
ERVFRD-1	Unknown
ERVW-1	Activation
GCM1
GFAP
JUND
MAPK8
MFSD2A	Unknown
MMP2
PGF	Activation
TNFRSF11A

JASPAR motifs

Motif	Name	Family
MA0646.1	GCM1	GCM
MA0646.2	GCM1	GCM

JASPAR matrix evidence (PMIDs): PMID:8962155

Upstream regulators (CollecTRI, top): AHR, CREB1, FOSL1, GCM1, HDAC3, HDAC5, JUNB, JUND, KAT7, KCNIP3, NFE2, POU2F1

miRNA regulators (miRDB)

58 targeting GCM1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4261	99.59	70.30	3415

Literature-anchored findings (GeneRIF, showing 39)

• GCMa regulates the syncytin-mediated trophoblastic fusion in human cells (PMID:12397062)
• Results suggest that GCM1 is a distinct transcription factor involved in placental disease and altered expression of the GCM1 gene may contribute to the etiology of pre-eclampsia. (PMID:15081636)
• GCM1 transcription factor expression is regulated both at the transcriptional and translational level and these studies show that the general features of GCM1 mRNA and protein expression in the human placenta are conserved with the mouse (PMID:15135239)
• the SCF(hFBW2) E3 complex has a key role in targeting hGCMa to the ubiquitin-proteasome degradation system (PMID:15640526)
• GCMa-driven syncytin expression is the key mechanism for syncytiotrophoblast formation (PMID:16004993)
• GCMa acetylation is mediated by CBP, which stimulates GCMa transcriptional activity through cyclic AMP/protein kinase A signaling (PMID:16166624)
• Results suggests that histone deacetylase 3 can functionally attenuate the CBP-upregulated GCMa activity in the activated signaling pathway leading to placental cell fusion. (PMID:16528103)
• Plasma placenta-specific 1 and GCM1 mRNAs appear promising as noninvasively measurable molecular markers for pre-eclampsia (PMID:16594548)
• GCMa is a new sumoylation substrate and its activity is down-regulated by sumoylation. (PMID:17646165)
• Ther is a functional role for GCM1 contributing to constitutively high trophoblast PGF expression and is the first direct evidence of an oxygen-responsive, trophoblast-specific transcription factor contributing to the regulation of PGF expression. (PMID:18160678)
• UBE2D2 is required for GCMa ubiquitination and for association with the SCF(FBXW2) complex. (PMID:18703417)
• A central role for GCM1 protein in mediating the differentiation of trophoblast cells along both the villous and extravillous pathways in human placental development. (PMID:19219068)
• Severe hypoxia is associated with reduced GCMa and syncytin-1 transcripts and altered fusion of primary trophoblasts. (PMID:19321927)
• CD9 increases GCM1 expression via the cAMP/PKA signaling pathway, resulting in the increase in ERVWE1 expression. (PMID:19692500)
• The researchers found evidence that GCM1 is a potential susceptibility or marker gene for IGA nephropathy. (PMID:19890582)
• Our results suggest that GCM1 is a critical factor in controlling placental cell fusion through transcriptional regulation of syncytin 2 and MFSD2A gene expression in placenta. (PMID:20484742)
• TIMP4 is a downstream target of GCM1. (PMID:21406447)
• Our study has identi fi ed a novel cAMP/Epac1/CaMKI/GCM1 signaling cascade that stimulates trophoblast fusion through promoting GCM1 phosphorylation and desumoylation. (PMID:21791615)
• Data show that beta-catenin/BCL9-Like (BCL9L)/T-cell factor 4 (TCF4) signalling directly targets the GCM1/syncytin pathway and thereby regulates the fusion of human choriocarcinoma cells. (PMID:22109522)
• these data demonstrate for the first time that GCMa is phosphorylated by the PKC- and MEK/extracellular signal-regulated kinase (ERK)-dependent mechanism, and that this phosphorylation is involved in its degradation process. (PMID:22206674)
• results support a role for reduced placental Gcm1 expression as a causative factor in defective syncytiotrophoblast differentiation and maternal and placental phenotypes in preeclampsia in humans. (PMID:22275534)
• study reveals a novel function of GCM1 and HtrA4 in regulation of trophoblast invasion and that abnormal HrtA4 expression may contribute to shallow trophoblast invasion in preeclampsia (PMID:22778138)
• Phorbol 12-myristate 13-acetate-induced protein kinase C and mitogen-activated protein kinase kinase/extracellular signal regulated kinase dependent pathway enhances the degradation as well as the transcriptional activity of GCMa. (PMID:22975632)
• GCM1-directed villous trophoblast differentiation is repressed by DREAM (PMID:23300953)
• c-Myc-regulated members of the miR-1792 and miR-106a363 clusters inhibit trophoblast differentiation by repressing GCM1 and CYP19A1. (PMID:23438603)
• Results suggest that caspase-14 may interact with GCM1 to participate in syncytiotrophoblast differentiation during placental development. (PMID:23580611)
• Gcm1 and Fzd5 function in an evolutionary conserved positive feedback loop that regulates trophoblast differentiation and sites of chorionic branching morphogenesis. (PMID:23610556)
• study reveals a novel function for RACK1 to regulate GCM1 activity and placental cell migration and invasion (PMID:23651062)
• reveals a positive feedback loop between glial cells missing 1 and Human chorionic gonadotropin regulating placental hCGbeta expression and cell differentiation (PMID:26503785)
• GLI2 stabilized glial cell missing-a, a pivotal transcriptional factor for trophoblastic syncytialization. (PMID:26769961)
• GATA3 knockdown elevated HtrA4 expression in BeWo and JEG-3 trophoblast cell lines and enhanced the invasion activities of both lines. This study uncovered a new GATA3 function in placenta as a negative regulator of GCM1 activity and trophoblastic invasion. (PMID:26899996)
• Twist1 may promote trophoblast syncytialization by regulating the expression of GCM1. (PMID:26992674)
• Identify a novel cis-acting sequence (-369 to -320) at the placental growth factor promoter, which was critical for mediating the basal and DLX3/GCM1-dependent PGF promoter activities. (PMID:27996093)
• results suggest that p45 NF-E2 negatively regulates differentiation and apoptosis activation of human syncytiotrophoblast by modulating GCM1 acetylation and sumoylation. (PMID:28383551)
• our studies demonstrate that DLX3 physically interacts with GCM1 and inhibits its transactivation activity, suggesting that DLX3 and GCM1 may form a complex to functionally regulate placental cell function through modulation of target gene expression. (PMID:28515447)
• Aberrant Gcm1 expression mediates Wnt/beta-catenin pathway activation in folate deficiency involved in neural tube defects. (PMID:33664222)
• Induction of the PPARgamma (Peroxisome Proliferator-Activated Receptor gamma)-GCM1 (Glial Cell Missing 1) Syncytialization Axis Reduces sFLT1 (Soluble fms-Like Tyrosine Kinase 1) in the Preeclamptic Placenta. (PMID:34024123)
• Functional antagonism between DeltaNp63alpha and GCM1 regulates human trophoblast stemness and differentiation. (PMID:35338152)
• The multifaceted role of GCM1 during trophoblast differentiation in the human placenta. (PMID:36442132)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gcm1	ENSMUSG00000023333
rattus_norvegicus	Gcm1	ENSRNOG00000007932
drosophila_melanogaster	gcm	FBGN0014179
drosophila_melanogaster	gcm2	FBGN0019809

Paralogs (1): GCM2 (ENSG00000124827)

Protein

Protein identifiers

Chorion-specific transcription factor GCMa — Q9NP62 (reviewed: Q9NP62)

Alternative names: GCM motif protein 1, Glial cells missing homolog 1

All UniProt accessions (1): Q9NP62

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in the control of expression of placental growth factor (PGF) and other placenta-specific genes. Binds to the trophoblast-specific element 2 (TSE2) of the aromatase gene enhancer. Binds to the SYDE1 promoter. Has a central role in mediating the differentiation of trophoblast cells along both the villous and extravillous pathways in placental development.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in the placenta. Expressed in trophoblast cells of the villi.

Post-translational modifications. Polyubiquitinated in the presence of UBE2D2 and FBXW2 (in vitro).

RefSeq proteins (1): NP_003634* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003902	Tscrpt_reg_GCM	Domain
IPR036115	GCM_dom_sf	Homologous_superfamily
IPR039791	GCM	Family
IPR043020	GCM_large	Homologous_superfamily
IPR043021	GCM_small	Homologous_superfamily

Pfam: PF03615

UniProt features (14 total): binding site 8, sequence conflict 2, chain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP62-F1	61.19	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 152; 154; 76; 82; 86; 113; 116; 125

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEUROGENESIS, MORF_RAD51L3, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, chr6p12, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, MORF_CTSB, NF1_Q6_01, GOBP_REGULATION_OF_SYNCYTIUM_FORMATION_BY_PLASMA_MEMBRANE_FUSION, MORF_IL4, MORF_PRKCA

GO Biological Process (13): syncytium formation by cell-cell fusion (GO:0000768), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), anatomical structure morphogenesis (GO:0009653), gliogenesis (GO:0042063), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), astrocyte fate commitment (GO:0060018), positive regulation of syncytium formation by plasma membrane fusion (GO:0060143), branching involved in labyrinthine layer morphogenesis (GO:0060670), cell differentiation involved in embryonic placenta development (GO:0060706), regulation of cell differentiation involved in embryonic placenta development (GO:0060800)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), histone deacetylase binding (GO:0042826), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cell-cell fusion	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
developmental process	1
anatomical structure development	1
neurogenesis	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
glial cell fate commitment	1
astrocyte differentiation	1
syncytium formation by cell-cell fusion	1
positive regulation of cellular component organization	1
regulation of syncytium formation by plasma membrane fusion	1
embryonic morphogenesis	1
labyrinthine layer morphogenesis	1
morphogenesis of a branching epithelium	1
embryonic placenta development	1
developmental process involved in reproduction	1
cell differentiation	1
regulation of cell differentiation	1
cell differentiation involved in embryonic placenta development	1
regulation of reproductive process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
enzyme binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1

Protein interactions and networks

STRING

941 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCM1	ERVW-1	Q9UQF0	638
GCM1	CDX2	Q99626	623
GCM1	ELF5	Q9UKW6	604
GCM1	ASCL2	Q99929	590
GCM1	PTH	P01270	587
GCM1	CGB5	P01233	582
GCM1	ESRRB	O95718	558
GCM1	CASR	P41180	554
GCM1	POU2F1	P14859	543
GCM1	DLX3	O60479	542
GCM1	ERVFRD-1	P60508	535
GCM1	PCDH12	Q9NPG4	497
GCM1	EOMES	O95936	497
GCM1	TFAP2C	Q92754	473
GCM1	PLAC1	Q9HBJ0	473

IntAct

35 interactions, top by confidence:

A	B	Type	Score
GCM1	HTRA4	psi-mi:“MI:0915”(physical association)	0.770
GCM1	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.770
HTRA4	GCM1	psi-mi:“MI:0915”(physical association)	0.770
FBXW2	RACK1	psi-mi:“MI:0914”(association)	0.680
GCM1	FBXW2	psi-mi:“MI:0915”(physical association)	0.610
GATA3	GCM1	psi-mi:“MI:0915”(physical association)	0.610
GCM1	GATA3	psi-mi:“MI:0915”(physical association)	0.610
GCM1	GATA3	psi-mi:“MI:0403”(colocalization)	0.610
GCM1	DLX3	psi-mi:“MI:0915”(physical association)	0.400
DLX3	GCM1	psi-mi:“MI:0915”(physical association)	0.400
PGF	GCM1	psi-mi:“MI:0915”(physical association)	0.400
GATA3	GCM1	psi-mi:“MI:0915”(physical association)	0.400
	GCM1	psi-mi:“MI:0915”(physical association)	0.370
CCL4L1	GCM1	psi-mi:“MI:0915”(physical association)	0.370
IL23A	GCM1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (87): CREBBP (Proximity Label-MS), SMARCA2 (Proximity Label-MS), EP300 (Proximity Label-MS), NCOA3 (Proximity Label-MS), TLE3 (Proximity Label-MS), BCL9 (Proximity Label-MS), ARID1A (Proximity Label-MS), KMT2D (Proximity Label-MS), ZNF609 (Proximity Label-MS), ZNF536 (Proximity Label-MS), KDM6A (Proximity Label-MS), TBL1X (Proximity Label-MS), NCOR1 (Proximity Label-MS), ATXN1L (Proximity Label-MS), HIVEP1 (Proximity Label-MS)

ESM2 similar proteins: A0A1B0GTH6, A0A1D5RMD1, A1KXM5, A2AEY4, A6NCI8, A6QQS3, A7KBS4, C4P6S0, O94713, P0C9Z7, P53963, P53976, Q0P670, Q0VAV2, Q10668, Q196W1, Q2KHR3, Q2YDJ5, Q32MG2, Q3V0A6, Q3V3Q4, Q4V8E9, Q5JRM2, Q68FV4, Q6AXV6, Q6AYN3, Q6NS59, Q7TSG5, Q80VJ6, Q80Y39, Q80YD3, Q810T2, Q86XD8, Q8C5U4, Q8CH19, Q8IWI9, Q8K4E0, Q8NDH2, Q8NEV8, Q8NFU7

Diamond homologs: O09102, O75603, P70348, Q27403, Q9NP62, Q9VLA2, Q9Z288

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CAMK1	“up-regulates activity”	GCM1	phosphorylation
SENP1	“up-regulates activity”	GCM1	desumoylation
FBXW2	“down-regulates quantity”	GCM1	binding
SCF-FBW2	“down-regulates quantity by destabilization”	GCM1	polyubiquitination
DUSP23	“up-regulates quantity by stabilization”	GCM1	dephosphorylation
GSK3B	“down-regulates quantity by destabilization”	GCM1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

880 predictions. Top by Δscore:

Variant	Effect	Δscore
6:53130801:AC:A	donor_gain	1.0000
6:53130802:CC:C	donor_gain	1.0000
6:53134070:A:AC	donor_gain	1.0000
6:53134071:C:CC	donor_gain	1.0000
6:53134071:CG:C	donor_gain	1.0000
6:53134071:CGCTG:C	donor_gain	1.0000
6:53145553:CATA:C	donor_loss	1.0000
6:53145554:ATAC:A	donor_loss	1.0000
6:53145555:TA:T	donor_loss	1.0000
6:53145764:TAGGG:T	acceptor_gain	1.0000
6:53145769:C:CC	acceptor_gain	1.0000
6:53148749:CTTA:C	donor_loss	1.0000
6:53148750:TTACC:T	donor_loss	1.0000
6:53148752:A:AG	donor_loss	1.0000
6:53148753:C:CA	donor_loss	1.0000
6:53128795:CT:C	acceptor_gain	0.9900
6:53128798:T:C	acceptor_gain	0.9900
6:53128798:T:TC	acceptor_gain	0.9900
6:53132025:T:TA	donor_gain	0.9900
6:53134320:ACGTT:A	acceptor_gain	0.9900
6:53134321:CGTT:C	acceptor_gain	0.9900
6:53134321:CGTTC:C	acceptor_gain	0.9900
6:53134322:GTT:G	acceptor_gain	0.9900
6:53134323:TT:T	acceptor_gain	0.9900
6:53134325:C:CC	acceptor_gain	0.9900
6:53134325:CT:C	acceptor_loss	0.9900
6:53134326:T:G	acceptor_loss	0.9900
6:53134328:A:AC	acceptor_gain	0.9900
6:53134328:A:C	acceptor_gain	0.9900
6:53145765:AGGG:A	acceptor_gain	0.9900

AlphaMissense

2897 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:53130911:A:C	H154Q	1.000
6:53130911:A:T	H154Q	1.000
6:53130925:C:G	G150R	1.000
6:53130925:C:T	G150R	1.000
6:53132037:C:A	W137C	1.000
6:53132037:C:G	W137C	1.000
6:53132039:A:G	W137R	1.000
6:53132039:A:T	W137R	1.000
6:53132040:G:C	F136L	1.000
6:53132040:G:T	F136L	1.000
6:53132042:A:G	F136L	1.000
6:53132050:A:T	V133D	1.000
6:53132073:G:C	C125W	1.000
6:53132074:C:T	C125Y	1.000
6:53132075:A:G	C125R	1.000
6:53132111:A:G	C113R	1.000
6:53134098:C:T	C101Y	1.000
6:53134099:A:G	C101R	1.000
6:53134101:A:T	I100N	1.000
6:53134107:G:T	P98H	1.000
6:53134156:A:G	C82R	1.000
6:53134168:C:G	G78R	1.000
6:53134172:G:C	C76W	1.000
6:53134173:C:T	C76Y	1.000
6:53134174:A:G	C76R	1.000
6:53134178:C:A	K74N	1.000
6:53134178:C:G	K74N	1.000
6:53134180:T:C	K74E	1.000
6:53134180:T:G	K74Q	1.000
6:53134181:C:A	K73N	1.000

dbSNP variants (sampled 300 via entrez): RS1000024893 (6:53126575 T>G), RS1000053844 (6:53139150 T>C), RS1000118359 (6:53148422 C>A,G), RS1000170273 (6:53148702 C>G,T), RS1000201701 (6:53150703 A>C), RS1000327724 (6:53139151 A>G), RS1000381545 (6:53139565 A>C), RS1000426337 (6:53145873 C>A,T), RS1000454942 (6:53135990 A>G), RS1000722447 (6:53142472 C>T), RS1000860835 (6:53146186 T>C), RS1000881336 (6:53134133 C>T), RS1000959716 (6:53128718 T>G), RS1000973901 (6:53127874 G>C), RS1001024856 (6:53127985 C>T)

Disease associations

OMIM: gene MIM:603715 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003072_3	Cerebrospinal fluid AB1-42 levels	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Colforsin	increases reaction, decreases expression, increases acetylation, affects localization, affects binding (+4 more)	4
Valproic Acid	decreases reaction, increases expression, increases methylation	3
Cadmium Chloride	increases expression, affects reaction, affects localization, decreases reaction, decreases expression	3
methylmercuric chloride	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases acetylation, increases activity, increases reaction	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases reaction, increases activity	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
27-hydroxycholesterol	decreases expression, decreases reaction	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
iodopravadoline	decreases reaction, decreases expression	1
monomethylarsonous acid	increases expression	1
T 0070907	decreases expression	1
licochalcone B	increases expression	1
Rosiglitazone	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Carmustine	increases expression	1
Chlorpyrifos	increases expression	1
Methapyrilene	decreases methylation	1
Dronabinol	decreases expression, decreases reaction	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XF88	Bewo31	Cancer cell line	Male

Clinical trials (associated diseases)

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