EFS

Summary

EFS (embryonal Fyn-associated substrate, HGNC:16898) is a protein-coding gene on chromosome 14q11.2, encoding Embryonal Fyn-associated substrate (O43281). Docking protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion.

The protein encoded by this gene is a member of the CAS (CRK-associated substrate) family of adaptor proteins which typically serve as scaffolds for the assembly of larger signaling complexes. These complexes form at the cell surface where integrin binding leads to the subsequent phosphorylation of a CAS protein. Additional binding of SRC family kinases leads to CAS hyperphosphorylation and the creation of binding sites for CRK and other proteins that cause actin cytoskeleton reorganization. This gene plays a role in integrin-mediated cell attachment, spreading, and migration and also plays a role in both normal and malignant cellular transformation. This broadly expressed gene has been shown to play a role in neurite outgrowth and its expression in the thymus and lymphocytes is important for T cell maturation and the development of immunological self-tolerance. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 10278 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 103 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 41 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.17 (unconstrained)
• MANE Select transcript: NM_005864
• Notable: 103 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16898
Approved symbol	EFS
Name	embryonal Fyn-associated substrate
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	EFS2, EFS1, HEFS, SIN, CASS3
Ensembl gene	ENSG00000100842
Ensembl biotype	protein_coding
OMIM	609906
Entrez	10278

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000216733

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1

ENST00000216733, ENST00000351354, ENST00000429593, ENST00000923553, ENST00000963506, ENST00001071521, ENST00001136276

RefSeq mRNA: 4 — MANE Select: NM_005864 NM_001277174, NM_001385607, NM_005864, NM_032459

CCDS: CCDS61404, CCDS9595, CCDS9596

Canonical transcript exons

ENST00000216733 — 6 exons

Exon	Start	End
ENSE00000653939	23358876	23358965
ENSE00000653940	23359317	23360039
ENSE00000889221	23360555	23360833
ENSE00001379666	23360141	23360281
ENSE00001951774	23356406	23357660
ENSE00003848739	23365008	23365172

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 97.16.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0478 / max 83.2694, expressed in 781 samples.

Highest expression (Bgee): ganglionic eminence, inferior vagus X ganglion, cervix squamous epithelium, mammalian vulva, embryo.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EFS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 41 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 59 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	9.4e-60	-0.85	14:23365968:T:C
Skin Not Sun Exposed Suprapubic	sqtl	1.2e-53	-0.91	14:23365968:T:C
Nerve Tibial	sqtl	1.5e-42	-0.83	14:23360833:T:C
Artery Tibial	sqtl	5.2e-38	-0.78	14:23355510:C:G
Esophagus Mucosa	sqtl	6.6e-34	-0.85	14:23365968:T:C
Adipose Subcutaneous	sqtl	1.2e-33	-0.74	14:23360839:T:G
Thyroid	sqtl	1.7e-32	-0.75	14:23354953:A:C
Breast Mammary Tissue	sqtl	6.6e-25	-0.80	14:23365968:T:C
Adipose Visceral Omentum	sqtl	3.2e-24	-0.73	14:23365968:T:C
Lung	sqtl	1.3e-20	-0.67	14:23354953:A:C
Artery Aorta	sqtl	4.8e-20	-0.74	14:23360833:T:C
Colon Sigmoid	sqtl	7.4e-20	+0.69	14:23365968:T:C
Esophagus Muscularis	sqtl	4.2e-17	-0.67	14:23354953:A:C
Skin Sun Exposed Lower leg	eqtl	4.8e-17	-0.26	14:23366863:C:T
Esophagus Gastroesophageal Junction	sqtl	5.0e-17	-0.74	14:23360833:T:C
Skin Not Sun Exposed Suprapubic	eqtl	5.8e-17	-0.31	14:23366863:C:T
Cells Cultured fibroblasts	sqtl	2.2e-14	-0.57	14:23365968:T:C
Esophagus Mucosa	eqtl	5.6e-14	-0.22	14:23366863:C:T
Prostate	sqtl	1.5e-12	-0.86	14:23354953:A:C
Testis	sqtl	3.7e-12	-0.67	14:23355510:C:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
142356	3.1983	710
142357	0.4556	320
142358	0.3939	126

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.16	gold quality
inferior vagus X ganglion	UBERON:0005363	96.87	gold quality
cervix squamous epithelium	UBERON:0006922	96.72	gold quality
mammalian vulva	UBERON:0000997	95.58	gold quality
embryo	UBERON:0000922	95.18	gold quality
ventricular zone	UBERON:0003053	95.18	gold quality
middle frontal gyrus	UBERON:0002702	95.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.12	gold quality
spinal cord	UBERON:0002240	95.08	gold quality
gingival epithelium	UBERON:0001949	94.67	gold quality
skin of abdomen	UBERON:0001416	94.54	gold quality
subthalamic nucleus	UBERON:0001906	94.48	gold quality
gingiva	UBERON:0001828	94.30	gold quality
skin of leg	UBERON:0001511	94.02	gold quality
skin of hip	UBERON:0001554	93.90	gold quality
zone of skin	UBERON:0000014	93.85	gold quality
nerve	UBERON:0001021	93.70	gold quality
tibial nerve	UBERON:0001323	93.70	gold quality
ectocervix	UBERON:0012249	93.64	gold quality
penis	UBERON:0000989	93.62	gold quality
medulla oblongata	UBERON:0001896	93.56	gold quality
endocervix	UBERON:0000458	93.32	gold quality
globus pallidus	UBERON:0001875	93.31	gold quality
lower esophagus mucosa	UBERON:0035834	93.26	gold quality
medial globus pallidus	UBERON:0002477	93.20	gold quality
upper leg skin	UBERON:0004262	93.20	gold quality
lateral globus pallidus	UBERON:0002476	93.12	gold quality
parotid gland	UBERON:0001831	92.90	gold quality
vagina	UBERON:0000996	92.84	gold quality
nipple	UBERON:0002030	92.74	gold quality
left ovary	UBERON:0002119	92.38	gold quality
superior vestibular nucleus	UBERON:0007227	92.35	gold quality
ventral tegmental area	UBERON:0002691	92.31	gold quality
uterine cervix	UBERON:0000002	92.28	gold quality
right ovary	UBERON:0002118	92.28	gold quality
inferior olivary complex	UBERON:0002127	91.96	gold quality
hair follicle	UBERON:0002073	91.86	gold quality
esophagus mucosa	UBERON:0002469	91.84	gold quality
body of uterus	UBERON:0009853	91.83	gold quality
midbrain	UBERON:0001891	91.81	gold quality
substantia nigra	UBERON:0002038	91.75	gold quality
tendon of biceps brachii	UBERON:0008188	91.72	gold quality
trigeminal ganglion	UBERON:0001675	91.60	gold quality
cervix epithelium	UBERON:0004801	91.58	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.44	gold quality
upper arm skin	UBERON:0004263	91.23	gold quality
pons	UBERON:0000988	91.21	gold quality
squamous epithelium	UBERON:0006914	91.21	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.20	gold quality
mammary duct	UBERON:0001765	90.88	gold quality
pharyngeal mucosa	UBERON:0000355	90.87	gold quality
prostate gland	UBERON:0002367	90.73	gold quality
epithelium of mammary gland	UBERON:0003244	90.60	gold quality
cortical plate	UBERON:0005343	90.50	gold quality
left uterine tube	UBERON:0001303	90.48	gold quality
dorsal root ganglion	UBERON:0000044	90.27	gold quality
ascending aorta	UBERON:0001496	90.21	gold quality
thoracic aorta	UBERON:0001515	90.16	gold quality
amygdala	UBERON:0001876	90.13	gold quality
cranial nerve II	UBERON:0000941	90.03	gold quality
oral cavity	UBERON:0000167	90.00	gold quality
urethra	UBERON:0000057	89.95	gold quality
esophagus	UBERON:0001043	89.91	gold quality
aorta	UBERON:0000947	89.78	gold quality
epithelium of esophagus	UBERON:0001976	89.76	gold quality
cartilage tissue	UBERON:0002418	89.75	gold quality
mouth mucosa	UBERON:0003729	89.62	gold quality
popliteal artery	UBERON:0002250	89.53	gold quality
descending thoracic aorta	UBERON:0002345	89.52	gold quality
tibial artery	UBERON:0007610	89.51	gold quality
saliva-secreting gland	UBERON:0001044	89.22	gold quality
right coronary artery	UBERON:0001625	89.21	gold quality
periodontal ligament	UBERON:0008266	89.20	gold quality
seminal vesicle	UBERON:0000998	89.16	gold quality
putamen	UBERON:0001874	89.16	gold quality
vena cava	UBERON:0004087	89.13	gold quality
left coronary artery	UBERON:0001626	89.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.06	gold quality
Ammon’s horn	UBERON:0001954	89.05	gold quality
esophagus squamous epithelium	UBERON:0006920	89.04	gold quality
placenta	UBERON:0001987	89.03	gold quality
coronary artery	UBERON:0001621	88.98	gold quality
minor salivary gland	UBERON:0001830	88.90	gold quality
trachea	UBERON:0003126	88.75	gold quality
ovary	UBERON:0000992	88.67	gold quality
sural nerve	UBERON:0015488	88.57	gold quality
mucosa of stomach	UBERON:0001199	88.29	gold quality
stromal cell of endometrium	CL:0002255	88.22	gold quality
lower esophagus	UBERON:0013473	87.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.96	gold quality
CA1 field of hippocampus	UBERON:0003881	87.88	gold quality
corpus callosum	UBERON:0002336	87.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.59	gold quality
female reproductive system	UBERON:0000474	87.57	gold quality
choroid plexus epithelium	UBERON:0003911	87.54	gold quality
tongue squamous epithelium	UBERON:0006919	87.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.31	gold quality
caudate nucleus	UBERON:0001873	87.28	gold quality
superior surface of tongue	UBERON:0007371	87.26	gold quality
myometrium	UBERON:0001296	87.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.83

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	55.8	low
Vagina	tissue	47.0	low
Nucleus accumbens	tissue	47.0
Hippocampus	tissue	43.3	medium
Locus coeruleus	tissue	40.0
Choroid plexus	tissue	38.3
Ovary	tissue	24.6	low
Esophagus	tissue	22.9	low
Prostate	tissue	21.4	medium
Seminal vesicle	tissue	21.2	low
Parathyroid gland	tissue	20.9	not detected
Endometrium 1	tissue	20.6	not detected
Postcentral gyrus	tissue	20.1
Salivary gland	tissue	19.2	low
Breast	tissue	15.5	medium
Cervix	tissue	15.2	low
Substantia nigra	tissue	11.9
Adrenal gland	tissue	11.9	not detected
Smooth muscle	tissue	11.7	not detected
Periaqueductal gray	tissue	11.6
Fallopian tube	tissue	11.5	not detected
Adipose tissue	tissue	11.1	not detected
Hypothalamus	tissue	10.0
Hippocampal formation	tissue	9.9
Retina	tissue	9.8
Placenta	tissue	9.8	low
Spinal cord	tissue	9.5
Epididymis	tissue	9.3	not detected
Pituitary gland	tissue	9.1
Olfactory bulb	tissue	8.9
Corpus callosum	tissue	8.3
Medulla oblongata	tissue	8.2
Gallbladder	tissue	8.2	medium
Midbrain	tissue	8.0
Amygdala	tissue	7.9
Pons	tissue	7.6
Urinary bladder	tissue	7.6	low
Thalamus	tissue	7.2
Superior colliculi	tissue	7.2
Septum	tissue	6.7
Lung	tissue	6.6	medium
Ventral forebrain	tissue	6.3
Basal ganglia	tissue	6.2	medium
Thyroid gland	tissue	5.7	not detected
Heart muscle	tissue	5.6	not detected
Cerebral cortex	tissue	5.5	medium
Insular cortex	tissue	5.5
Spleen	tissue	5.3	not detected
Appendix	tissue	5.2	not detected
Putamen	tissue	5.1
Entorhinal cortex	tissue	4.9
Temporal cortex	tissue	4.9
Retrosplenial cortex	tissue	4.8
Tongue	tissue	4.7
Tonsil	tissue	4.5	low
Somatosensory cortex	tissue	4.5
Motor cortex	tissue	4.4
Caudate putamen	tissue	4.3
Frontal cortex	tissue	4.2
Small intestine	tissue	4.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (133.9), Temporal white matter (127.9), Nucleus raphe obscurus (112.9), Cerebellar white matter (108.9), Globus pallidus, externus (104.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting EFS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 54 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-32-3P	99.36	68.20	2517

Functional genomics

gnomAD constraint: pLI 7.22e-11, LOEUF 1.17, missense Z -0.398 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000216733 — one region, missense o/e 0.98.

Literature-anchored findings (GeneRIF, showing 4)

• Analysis of 16 Uveal melanoma showed full methylation of the EFS CpG island in 8 (50%), no methylation in 5(31%)and partial methylation in 3 (19%)tumors. Kaplan-Meier analysis revealed higher risk of metastatic progression for tumors with EFS methylation. (PMID:21871071)
• we suggest that EFS should be considered as a novel tumor suppressor gene in prostate cancer. (PMID:25296736)
• EFS and CASS4 protein function in the context of the larger CAS family group. [Review] (PMID:26119091)
• The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial-like head and neck carcinoma subtypes. (PMID:30652380)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	efs	ENSDARG00000088835
mus_musculus	Efs	ENSMUSG00000022203
rattus_norvegicus	Efs	ENSRNOG00000042029
drosophila_melanogaster	p130CAS	FBGN0035101

Paralogs (3): BCAR1 (ENSG00000050820), CASS4 (ENSG00000087589), NEDD9 (ENSG00000111859)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:105311) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased inflammatory response	1
kidney inflammation	1
liver inflammation	1
lung inflammation	1
abnormal T cell physiology	1
increased immunoglobulin level	1
increased IgG level	1
increased IgA level	1
small intestinal inflammation	1
increased interferon-gamma secretion	1
abnormal interleukin secretion	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0P5B1	92.6%	Diamond
Canis lupus familiaris	A0A8I3PDQ1	88.7%	Diamond
Sus scrofa	A5GFW5	71.5%	Diamond
Schizosaccharomyces pombe 972h-	Q9URW6	49.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RNF212B	protein-coding	100507650
SLC22A17	protein-coding	51310
HOMEZ	protein-coding	57594
BCL2L2	protein-coding	599
PABPN1	protein-coding	8106
PPP1R3E	protein-coding	90673
MHRT	ncRNA	104564225
MIR208A	ncRNA	406990
MYH6	protein-coding	4624
MYH7	protein-coding	4625
IL25	protein-coding	64806
BCL2L2-PABPN1	protein-coding	100529063
CMTM5	protein-coding	116173

Protein

Protein identifiers

Embryonal Fyn-associated substrate — O43281 (reviewed: O43281)

Alternative names: Cas scaffolding protein family member 3

All UniProt accessions (1): O43281

UniProt curated annotations — full annotation on UniProt →

Function. Docking protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. May serve as an activator of SRC and a downstream effector. Interacts with the SH3 domain of FYN and with CRK, SRC, and YES.

Tissue specificity. The protein has been detected in lung and placenta.

Post-translational modifications. Phosphorylated on multiple tyrosine residues. Phosphorylated on tyrosines by FYN and SRC.

Domain organisation. Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL SH2 domains. The SH3-binding sites that bind to the SRC SH3 domain are required for interaction with CRK and are implicated in promotion of serum response element (SRE) activation. The SH3 domain interacts with PTK2/FAK1.

Similarity. Belongs to the CAS family.

Isoforms (3)

UniProt ID	Names	Canonical?
O43281-1	Efs1	yes
O43281-2	Efs2
O43281-3	3

RefSeq proteins (4): NP_001264103, NP_001372536, NP_005855, NP_115835 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR021901	CAS_C	Domain
IPR035747	EFS_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR037362	CAS_fam	Family

Pfam: PF12026, PF14604

UniProt features (18 total): region of interest 5, compositionally biased region 3, sequence variant 3, splice variant 2, short sequence motif 2, chain 1, domain 1, modified residue 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43281-F1	61.71	0.30

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF uncertain

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)

Type	Positions
Phosphotyrosine	253

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 116 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, JAEGER_METASTASIS_DN, MODULE_45, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, CHANDRAN_METASTASIS_DN, CAGCTG_AP4_Q5, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, MODULE_66, BLALOCK_ALZHEIMERS_DISEASE_UP, WONG_ENDMETRIUM_CANCER_DN, SCHLOSSER_SERUM_RESPONSE_DN, MODULE_88, ONGUSAHA_TP53_TARGETS, CCCNNGGGAR_OLF1_01, MODULE_11

GO Biological Process (4): cell adhesion (GO:0007155), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell migration (GO:0016477), intracellular signal transduction (GO:0035556)

GO Molecular Function (3): SH3 domain binding (GO:0017124), protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), focal adhesion (GO:0005925), plasma membrane (GO:0005886)

GO top-level categories

12 GO namespaces:

Category	Terms
intracellular anatomical structure	2
cellular process	1
enzyme-linked receptor protein signaling pathway	1
cell motility	1
signal transduction	1
protein domain specific binding	1
protein binding	1
binding	1
cellular anatomical structure	1
cell-substrate junction	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
protein domain specific binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 885 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EFS	CASP3	P42574	718
EFS	CSE1L	P55060	590
EFS	BCL2	P10415	570
EFS	BAX	P55269	570
EFS	ANXA5	P08758	507
EFS	ACR	P10323	498
EFS	CASZ1	Q86V15	494
EFS	CASP9	P55211	470
EFS	TP53	P04637	435
EFS	ACTB	P02570	430
EFS	CYCS	P00001	428
EFS	GAPDH	P00354	428
EFS	PARP1	P09874	424
EFS	PRIMA1	Q86XR5	414
EFS	CNTN4	Q8IWV2	359

IntAct

Human interaction partners of EFS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

Partner	Interaction type	MIscore	Records
ABI2	physical association	0.740	6
BLK	physical association	0.710	5
FYN	physical association	0.670	5
NUP155	physical association	0.560	3
OSTF1	physical association	0.560	3
SORBS2	physical association	0.560	3
TSSK1B	physical association	0.560	3
ZNF417	physical association	0.560	3
SH2D3C	physical association	0.550	2
ABL1	physical association	0.400	1
CRK	physical association	0.400	1
GRB2	physical association	0.400	1
NCK1	physical association	0.400	1
PIK3R1	physical association	0.400	1
PLCG1	physical association	0.400	1
SRC	physical association	0.400	1
BDKRB2	physical association	0.370	1
NCK2	physical association	0.370	1
NF1	physical association	0.370	1
SORBS3	physical association	0.370	1
TRAPPC6A	physical association	0.370	1
BCAR1	physical association	0.000	1

BioGRID (51 interactions; top human partners by supporting records): FYN (Two-hybrid; 4 records), ABI2 (Two-hybrid; 3 records), BLK (Two-hybrid; 3 records), SRC (Protein-peptide; 3 records), OSTF1 (Two-hybrid; 2 records), SORBS2 (Two-hybrid; 2 records), TRAPPC6A (Two-hybrid; 2 records), TSSK1B (Two-hybrid; 2 records), AGXT (Two-hybrid), APP (Reconstituted Complex), BCAR1 (Two-hybrid), BDKRB2 (Two-hybrid), CRK (Far Western), GLMN (Two-hybrid), GPANK1 (Two-hybrid)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	8	160.3×	2e-14
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	93.9×	1e-07
RHOU GTPase cycle	5	73.3×	4e-07
FCGR3A-mediated phagocytosis	7	69.0×	5e-10
VEGFA-VEGFR2 Pathway	8	58.6×	6e-11
Regulation of actin dynamics for phagocytic cup formation	5	48.5×	2e-06
RAF/MAP kinase cascade	5	16.1×	1e-04
Signaling by Receptor Tyrosine Kinases	5	13.6×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	93.8×	1e-08
epidermal growth factor receptor signaling pathway	6	67.6×	6e-08
cell migration	6	16.8×	8e-05

Disease & clinical

Genetic variants

Variant evidence for EFS: 103 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	3
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 445):

Position(s)	Effect	Δscore	Sites
14:23360139–23360140	donor_loss	1.0000	2
14:23365006–23365007	donor_loss	1.0000	4
14:23359315–23359316	donor_loss	0.9900	5
14:23360139–23360140	donor_loss	0.9900	3
14:23360282–23360283	acceptor_loss	0.9900	5
14:23365007	donor_loss	0.9900
14:23360282	acceptor_loss	0.9800
14:23360553–23360554	donor_loss	0.9700	3
14:23359071	donor_gain	0.9600
14:23360040–23360041	acceptor_loss	0.9600	6

AlphaMissense

549 missense substitutions predicted likely pathogenic (of 3,526 scored), across 171 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F26	8	0.975	0.997
N16	8	0.928	0.993
D30	8	0.927	0.976
F470	8	0.859	0.954
W46	7	0.974	0.995
E23	7	0.961	0.980
R62	7	0.961	0.993
C49	7	0.939	0.990
D15	7	0.913	0.973
N61	7	0.898	0.978
F552	7	0.878	0.967
F486	7	0.870	0.968
D432	7	0.789	0.860
E19	7	0.768	0.901
D489	7	0.756	0.863
G56	6	0.970	0.992
P59	6	0.951	0.988
G29	6	0.943	0.981
V58	6	0.882	0.992
A12	6	0.834	0.973

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000202

Disease associations

OMIM: gene MIM:609906 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases methylation, affects cotreatment	9
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
bisphenol A	affects cotreatment, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
propionic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arbutin	decreases expression	1
Arsenic	increases abundance, decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Progesterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1
tert-Butylhydroperoxide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.