LY6G6F

Summary

LY6G6F (lymphocyte antigen 6 family member G6F, HGNC:13933) is a protein-coding gene on chromosome 6p21.33, encoding Lymphocyte antigen 6 complex locus protein G6f (Q5SQ64). May play a role in the downstream signal transduction pathways involving GRB2 and GRB7.

The human G6f protein is a type I transmembrane protein belonging to the immunoglobin (Ig) superfamily, which is comprised of cell-surface proteins involved in the immune system and cellular recognition (de Vet et al., 2003 [PubMed 12852788]).

Source: NCBI Gene 259215 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_001003693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13933
Approved symbol	LY6G6F
Name	lymphocyte antigen 6 family member G6F
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	G6f, NG32
Ensembl gene	ENSG00000204424
Ensembl biotype	protein_coding
OMIM	611404
Entrez	259215

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000375832

RefSeq mRNA: 1 — MANE Select: NM_001003693 NM_001003693

CCDS: CCDS34403

Canonical transcript exons

ENST00000375832 — 6 exons

Exon	Start	End
ENSE00001617798	31710352	31710418
ENSE00001726559	31706866	31706958
ENSE00001770083	31710567	31710679
ENSE00003491320	31710026	31710181
ENSE00003536928	31707871	31708134
ENSE00003656192	31707458	31707787

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 92.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0473 / max 14.6976, expressed in 16 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67024	0.0870	31
67029	0.0473	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	92.68	gold quality
leukocyte	CL:0000738	91.48	gold quality
blood	UBERON:0000178	79.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.15	gold quality
granulocyte	CL:0000094	75.11	gold quality
bone marrow	UBERON:0002371	61.75	gold quality
right lung	UBERON:0002167	60.75	gold quality
bone marrow cell	CL:0002092	56.53	silver quality
spleen	UBERON:0002106	55.27	gold quality
lower esophagus mucosa	UBERON:0035834	54.84	gold quality
right lobe of thyroid gland	UBERON:0001119	53.79	gold quality
right uterine tube	UBERON:0001302	52.63	gold quality
upper lobe of left lung	UBERON:0008952	50.88	gold quality
thyroid gland	UBERON:0002046	50.74	gold quality
ganglionic eminence	UBERON:0004023	49.46	gold quality
left lobe of thyroid gland	UBERON:0001120	49.22	gold quality
lung	UBERON:0002048	48.85	gold quality
placenta	UBERON:0001987	45.19	gold quality
sural nerve	UBERON:0015488	42.52	gold quality
skin of leg	UBERON:0001511	41.87	gold quality
zone of skin	UBERON:0000014	41.61	gold quality
ventricular zone	UBERON:0003053	41.15	gold quality
skin of abdomen	UBERON:0001416	40.78	gold quality
esophagus mucosa	UBERON:0002469	39.83	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
fallopian tube	UBERON:0003889	37.07	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
rectum	UBERON:0001052	35.84	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
duodenum	UBERON:0002114	33.28	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	21.18
E-HCAD-10	yes	16.53
E-MTAB-9221	yes	16.17
E-HCAD-1	yes	5.04
E-ANND-3	no	2.55

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• G6f recruits adaptor signalling proteins Grb2 and Grb7. (PMID:12852788)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ly6g6f	ENSMUSG00000034923

Paralogs (1): LY6G6D (ENSG00000244355)

Protein

Protein identifiers

Lymphocyte antigen 6 complex locus protein G6f — Q5SQ64 (reviewed: Q5SQ64)

All UniProt accessions (2): A0A1L6Z9Z3, Q5SQ64

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the downstream signal transduction pathways involving GRB2 and GRB7.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with GRB2 and GRB7 in a phosphorylation-dependent manner.

Subcellular location. Cell membrane.

Post-translational modifications. N-glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5SQ64-1	1	yes
Q5SQ64-2	2

RefSeq proteins (1): NP_001003693* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR026524	LY6G6d/LY6G6f	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686

UniProt features (15 total): sequence variant 4, topological domain 2, signal peptide 1, chain 1, mutagenesis site 1, transmembrane region 1, domain 1, modified residue 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SQ64-F1	77.31	0.40

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 (1): 281

Disulfide bonds (1): 35–106

Glycosylation sites (1): 88

Mutagenesis-validated functional residues (1):

Position	Phenotype
281	no phosphorylation. no interaction with grb2 and grb7. no phosphorylation increase of p42/44 map kinase.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 92 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOCC_CELL_SURFACE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, MARTINEZ_RB1_TARGETS_DN, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, TGANTCA_AP1_C, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_RESPONSE_TO_ACETYLCHOLINE, NKX25_01, GOCC_FILOPODIUM

GO Biological Process (0):

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

GO Cellular Component (3): plasma membrane (GO:0005886), platelet alpha granule membrane (GO:0031092), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1
secretory granule membrane	1
platelet alpha granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LY6G6F	GRB7	Q14451	839
LY6G6F	A0A0B4J1T7	A0A0B4J1T7	690
LY6G6F	LY6G6C	O95867	668
LY6G6F	LY6L	H3BQJ8	621
LY6G6F	MPIG6B	O95866	620
LY6G6F	LY6G5B	Q8NDX9	609
LY6G6F	PATE3	B3GLJ2	604
LY6G6F	PINLYP	A6NC86	577
LY6G6F	PATE2	Q6UY27	570
LY6G6F	LY6G5C	Q5SRR4	570
LY6G6F	LYPD5	Q6UWN5	529
LY6G6F	PATE4	P0C8F1	525
LY6G6F	PATE1	Q8WXA2	522
LY6G6F	LY6G6D	O95868	512
LY6G6F	LYPD4	Q6UWN0	507

IntAct

7 interactions, top by confidence:

A	B	Type	Score
GRB2	LY6G6F	psi-mi:“MI:0915”(physical association)	0.590
LY6G6F	GRB2	psi-mi:“MI:0915”(physical association)	0.590
LY6G6F	GRB7	psi-mi:“MI:0915”(physical association)	0.520
GRB7	LY6G6F	psi-mi:“MI:0915”(physical association)	0.520
LY6G6F	KCTD10	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): LY6G6F (Reconstituted Complex), LY6G6F (Reconstituted Complex), LY6G6F (Affinity Capture-Western), LY6G6F (Affinity Capture-Western), KCTD10 (Affinity Capture-MS), GOPC (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5C7, A5D7H1, A6H7A0, A6NJW4, A6QLN9, A8MUP2, A8MXK1, B0BMW8, B0BNL6, O35393, O62657, O75078, P52875, P55244, P56880, P57791, Q08334, Q0V881, Q15768, Q16557, Q2M1K6, Q3SZQ2, Q3UHH2, Q4V899, Q5E9H2, Q5FYB0, Q5M7U7, Q5R6I6, Q5RCI5, Q5SQ64, Q642A6, Q6PCB0, Q7TPB4, Q8BM89, Q8BZH0, Q8N431, Q8N5I2, Q8R2R5, Q8R2Z5, Q8VE98

Diamond homologs: Q0V881, Q5SQ64, Q6MG56

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	60
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1216 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31707969:G:GT	donor_gain	1.0000
6:31707974:G:T	donor_gain	1.0000
6:31710006:T:TA	acceptor_gain	1.0000
6:31710065:C:CA	acceptor_gain	1.0000
6:31710066:G:A	acceptor_gain	1.0000
6:31715621:AACCG:A	donor_loss	1.0000
6:31715622:ACCG:A	donor_loss	1.0000
6:31715623:CC:C	donor_gain	1.0000
6:31715624:CGTG:C	donor_loss	1.0000
6:31715625:G:GG	donor_gain	1.0000
6:31715625:GTGA:G	donor_loss	1.0000
6:31707679:T:TA	acceptor_gain	0.9900
6:31707970:A:T	donor_gain	0.9900
6:31707974:G:GT	donor_gain	0.9900
6:31710011:T:TA	acceptor_gain	0.9900
6:31710064:AC:A	acceptor_gain	0.9900
6:31710064:ACG:A	acceptor_gain	0.9900
6:31715622:ACC:A	donor_gain	0.9900
6:31715626:TGA:T	donor_loss	0.9900
6:31715627:G:GT	donor_loss	0.9900
6:31715628:AGT:A	donor_loss	0.9900
6:31707787:GGTG:G	donor_loss	0.9800
6:31707788:GT:G	donor_loss	0.9800
6:31707789:T:G	donor_loss	0.9800
6:31708014:A:AG	donor_gain	0.9800
6:31708015:G:GG	donor_gain	0.9800
6:31710007:G:A	acceptor_gain	0.9800
6:31710012:G:A	acceptor_gain	0.9800
6:31710024:A:AG	acceptor_gain	0.9800
6:31710025:G:GG	acceptor_gain	0.9800

AlphaMissense

1908 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31707965:G:C	W159C	0.994
6:31707965:G:T	W159C	0.994
6:31707963:T:A	W159R	0.990
6:31707963:T:C	W159R	0.990
6:31708122:T:C	F212L	0.987
6:31708124:T:A	F212L	0.987
6:31708124:T:G	F212L	0.987
6:31707552:G:C	W49C	0.986
6:31707552:G:T	W49C	0.986
6:31707550:T:A	W49R	0.985
6:31707550:T:C	W49R	0.985
6:31707715:T:G	Y104D	0.981
6:31707677:T:C	L91S	0.978
6:31708123:T:G	F212C	0.978
6:31707721:T:A	C106S	0.977
6:31707722:G:C	C106S	0.977
6:31707720:G:C	W105C	0.974
6:31707720:G:T	W105C	0.974
6:31708092:T:C	C202R	0.974
6:31708123:T:C	F212S	0.972
6:31707924:T:C	C146R	0.971
6:31707723:C:G	C106W	0.970
6:31707759:G:C	W118C	0.970
6:31707759:G:T	W118C	0.970
6:31707924:T:A	C146S	0.970
6:31707925:G:C	C146S	0.970
6:31708092:T:A	C202S	0.970
6:31708093:G:C	C202S	0.970
6:31707721:T:C	C106R	0.969
6:31708030:T:C	L181P	0.967

dbSNP variants (sampled 300 via entrez): RS1000387479 (6:31707808 C>A), RS1001054854 (6:31708875 A>G), RS1001727819 (6:31705200 A>G), RS1001780258 (6:31704876 C>A,T), RS1002417139 (6:31706888 A>G), RS1003857525 (6:31706696 G>A), RS1003895741 (6:31706045 C>G,T), RS1004246220 (6:31706272 T>C), RS1004564869 (6:31708361 A>G), RS1005408839 (6:31705102 C>T), RS1005606458 (6:31707280 A>C), RS1006356122 (6:31705109 C>T), RS1006961267 (6:31705577 C>T), RS1007196588 (6:31709845 G>A), RS1007248815 (6:31709528 G>A,T)

Disease associations

OMIM: gene MIM:611404 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_281	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST010725_43	Malaria	5.000000e-07
GCST010725_62	Malaria	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Nitrogen Dioxide	affects methylation, increases abundance	1
Particulate Matter	increases abundance, affects methylation	1

Clinical trials (associated diseases)

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