GAB4

Summary

GAB4 (GRB2 associated binding protein family member 4, HGNC:18325) is a protein-coding gene on chromosome 22q11.1, encoding GRB2-associated-binding protein 4 (Q2WGN9).

Predicted to enable transmembrane receptor protein tyrosine kinase adaptor activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm.

Source: NCBI Gene 128954 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 107 total
• Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
• MANE Select transcript: NM_001037814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18325
Approved symbol	GAB4
Name	GRB2 associated binding protein family member 4
Location	22q11.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000215568
Ensembl biotype	protein_coding
Entrez	128954

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000400588, ENST00000465611, ENST00000520505, ENST00000523144, ENST00000643316, ENST00000651146

RefSeq mRNA: 2 — MANE Select: NM_001037814 NM_001037814, NM_001366857

CCDS: CCDS42976

Canonical transcript exons

ENST00000400588 — 10 exons

Exon	Start	End
ENSE00001543665	16961936	16962876
ENSE00001543672	16966100	16966364
ENSE00001543676	16969943	16970193
ENSE00001543677	16987960	16988167
ENSE00001543684	17007941	17008222
ENSE00003465094	16965178	16965268
ENSE00003541852	16963725	16963829
ENSE00003567406	16964766	16964862
ENSE00003654045	16968298	16968383
ENSE00003670539	16991873	16992176

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 81.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0296 / max 17.5923, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193062	0.0296	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.89	gold quality
left testis	UBERON:0004533	64.77	gold quality
right testis	UBERON:0004534	64.02	gold quality
testis	UBERON:0000473	63.30	gold quality
sural nerve	UBERON:0015488	63.20	silver quality
myocardium	UBERON:0002349	53.86	gold quality
tibial nerve	UBERON:0001323	49.24	gold quality
colonic epithelium	UBERON:0000397	48.86	gold quality
tendon of biceps brachii	UBERON:0008188	47.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.13	gold quality
adult organism	UBERON:0007023	45.99	gold quality
spinal cord	UBERON:0002240	45.55	gold quality
buccal mucosa cell	CL:0002336	45.37	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
substantia nigra	UBERON:0002038	41.30	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
midbrain	UBERON:0001891	41.08	gold quality
esophagus squamous epithelium	UBERON:0006920	41.06	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting GAB4, 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-6077	99.99	68.04	2299
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-595	98.25	67.44	699
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-4693-3P	95.23	65.92	735
HSA-MIR-4268	94.45	64.09	819

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	dos	FBGN0016794
caenorhabditis_elegans		WBGENE00004928

Paralogs (7): PHLDB1 (ENSG00000019144), GAB2 (ENSG00000033327), GAB1 (ENSG00000109458), PHLDB2 (ENSG00000144824), PLEKHS1 (ENSG00000148735), GAB3 (ENSG00000160219), PHLDB3 (ENSG00000176531)

Protein

Protein identifiers

GRB2-associated-binding protein 4 — Q2WGN9 (reviewed: Q2WGN9)

Alternative names: GRB2-associated binder 2-like, GRB2-associated binder 4, GRB2-associated-binding protein 2-like, Growth factor receptor bound protein 2-associated protein 4

All UniProt accessions (4): Q2WGN9, A0A2R8Y714, A0A494C132, H0YB31

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the GAB family.

RefSeq proteins (2): NP_001032903, NP_001353786 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR046355	Gab1-4-like	Family

Pfam: PF00169

UniProt features (13 total): compositionally biased region 5, region of interest 5, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2WGN9-F1	54.53	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_CELL_SURFACE_RECEPTOR_PROTEIN_TYROSINE_KINASE_SIGNALING_PATHWAY, GOMF_KINASE_BINDING, GOMF_SIGNALING_RECEPTOR_COMPLEX_ADAPTOR_ACTIVITY, GOMF_PROTEIN_TYROSINE_KINASE_BINDING, GOMF_SIGNALING_ADAPTOR_ACTIVITY, CERIBELLI_GENES_INACTIVE_AND_BOUND_BY_NFY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_TRANSMEMBRANE_RECEPTOR_PROTEIN_TYROSINE_KINASE_ADAPTOR_ACTIVITY, GOMF_RECEPTOR_TYROSINE_KINASE_BINDING, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY, MIR6827_5P, MIR595, MIR4751, GSE13485_CTRL_VS_DAY1_YF17D_VACCINE_PBMC_DN

GO Biological Process (2): signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169)

GO Molecular Function (1): transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
signaling receptor complex adaptor activity	1
receptor tyrosine kinase binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAB4	LRRC74B	Q6ZQY2	548
GAB4	RIMBP3C	A6NJZ7	530
GAB4	CCT8L2	Q96SF2	517
GAB4	GRB2	P29354	503
GAB4	C2CD4D	B7Z1M9	479
GAB4	OR2B11	Q5JQS5	433
GAB4	ZSCAN30	Q86W11	431
GAB4	A1BG	P04217	399
GAB4	MTNAP1	Q9BSJ5	392
GAB4	CRKL	P46109	380
GAB4	LRRC74A	Q0VAA2	350
GAB4	DCAF4L2	Q8NA75	348
GAB4	PTPN11	Q06124	338
GAB4	CD28	P10747	333
GAB4	GAB2	Q9UQC2	322

IntAct

0 interactions, top by confidence:

BioGRID (1): GAB4 (Affinity Capture-MS)

ESM2 similar proteins: A0JPN4, A6NP61, A8MVX0, B2RQL2, D2J0Y4, E9Q2Z1, O35181, O43734, O88286, O88850, P0DW16, P28322, P43268, P56975, P86174, P97303, Q01954, Q1W617, Q1XFL1, Q2WGN9, Q3TQ03, Q3USH1, Q498S6, Q4G112, Q4V7B1, Q5D1E7, Q69ZB8, Q6A098, Q6ZU67, Q6ZVD7, Q76N89, Q7Z7G1, Q8BIY3, Q8BW86, Q8IUC6, Q8K4P8, Q8N365, Q8N7N6, Q8NA82, Q93075

Diamond homologs: A6QLU3, Q00IB7, Q13480, Q2WGN9, Q86SQ0, Q8BUL6, Q8K1N2, Q8WWW8, Q99PF6, Q9EQH1, Q9HB21, Q9QYY0, Q9ULM0, Q9UQC2, Q9VZZ9, Q9W5D0, Q9Z1S8, Q3ZBA3, Q86IV4, Q8BSM5, Q9ERS5, Q9HB19, P54644, Q1ZXL0, Q559T8, Q55GV3, Q5U2Z7, Q6Q308, Q8C115, Q8C2K1, Q8IVE3, Q8N264, Q9NYT0, Q9QXT1, Q9ST43, Q9UN19, Q9WV52, A8JQ65, B4I4Y1, B4PRE2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2192 predictions. Top by Δscore:

Variant	Effect	Δscore
22:16965175:CA:C	donor_loss	1.0000
22:16965176:ACCT:A	donor_loss	1.0000
22:16965264:GTTGG:G	acceptor_gain	1.0000
22:16965265:TTGG:T	acceptor_gain	1.0000
22:16965266:TGG:T	acceptor_gain	1.0000
22:16965267:GG:G	acceptor_gain	1.0000
22:16965267:GGC:G	acceptor_loss	1.0000
22:16965269:C:CC	acceptor_gain	1.0000
22:16965269:C:G	acceptor_loss	1.0000
22:16965275:C:CT	acceptor_gain	1.0000
22:16965276:A:T	acceptor_gain	1.0000
22:16991973:A:AC	donor_gain	1.0000
22:16991974:C:CC	donor_gain	1.0000
22:16991974:CTGGT:C	donor_gain	1.0000
22:16991994:ATAGC:A	donor_gain	1.0000
22:17007939:A:AC	donor_gain	1.0000
22:17007940:C:CC	donor_gain	1.0000
22:17007940:CA:C	donor_gain	1.0000
22:17007940:CAAAG:C	donor_gain	1.0000
22:17007943:AGAG:A	donor_gain	1.0000
22:17007952:G:C	donor_gain	1.0000
22:17007955:T:TA	donor_gain	1.0000
22:17007973:T:TA	donor_gain	1.0000
22:16962872:GATGG:G	acceptor_gain	0.9900
22:16962873:ATGG:A	acceptor_gain	0.9900
22:16962874:TGG:T	acceptor_gain	0.9900
22:16962875:GG:G	acceptor_gain	0.9900
22:16962877:C:CC	acceptor_gain	0.9900
22:16962877:C:CG	acceptor_loss	0.9900
22:16963803:G:T	acceptor_gain	0.9900

AlphaMissense

3790 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:16991922:C:A	W143C	0.999
22:16991922:C:G	W143C	0.999
22:16991924:A:G	W143R	0.999
22:16991924:A:T	W143R	0.999
22:16991961:A:C	F130L	0.999
22:16991961:A:T	F130L	0.999
22:16991963:A:G	F130L	0.999
22:16992156:A:C	F65L	0.999
22:16992156:A:T	F65L	0.999
22:16992157:A:G	F65S	0.999
22:16992158:A:G	F65L	0.999
22:16991956:A:G	L132P	0.998
22:16991988:A:C	F121L	0.998
22:16991988:A:T	F121L	0.998
22:16991989:A:G	F121S	0.998
22:16991990:A:G	F121L	0.998
22:16992110:A:G	Y81H	0.998
22:16992171:C:A	W60C	0.998
22:16992171:C:G	W60C	0.998
22:16992173:A:G	W60R	0.998
22:16992173:A:T	W60R	0.998
22:16991923:C:G	W143S	0.997
22:16992115:A:G	L79P	0.997
22:16992161:A:G	W64R	0.997
22:16992161:A:T	W64R	0.997
22:16991950:G:T	A134D	0.996
22:16991962:A:G	F130S	0.996
22:16991989:A:C	F121C	0.995
22:16992070:A:C	I94S	0.995
22:16992070:A:T	I94N	0.995

dbSNP variants (sampled 300 via entrez): RS1000020296 (22:16998850 G>C,T), RS1000247177 (22:16987277 C>T), RS1000274392 (22:16992552 C>T), RS1000383515 (22:16986922 C>T), RS1000445814 (22:16992952 C>T), RS1000533206 (22:17004714 A>T), RS1000636848 (22:17009011 C>T), RS1000650318 (22:16974496 G>A), RS1000725758 (22:16980400 G>T), RS1000748512 (22:16974104 G>A), RS1001113293 (22:17003442 C>G,T), RS1001255715 (22:16985710 A>G), RS1001294990 (22:16978793 G>A), RS1001355104 (22:16997822 A>G), RS1001369601 (22:16991382 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	1
Phthalic Acids	decreases methylation	1

Clinical trials (associated diseases)

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