SARAF

Summary

SARAF (store-operated calcium entry associated regulatory factor, HGNC:28789) is a protein-coding gene on chromosome 8p12, encoding Store-operated calcium entry-associated regulatory factor (Q96BY9). Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling.

Involved in regulation of store-operated calcium entry. Located in endoplasmic reticulum membrane and endoplasmic reticulum-plasma membrane contact site.

Source: NCBI Gene 51669 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• MANE Select transcript: NM_016127

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28789
Approved symbol	SARAF
Name	store-operated calcium entry associated regulatory factor
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	MGC8721
Ensembl gene	ENSG00000133872
Ensembl biotype	protein_coding
OMIM	614768
Entrez	51669

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000256255, ENST00000517569, ENST00000518174, ENST00000518296, ENST00000518340, ENST00000520303, ENST00000521083, ENST00000521265, ENST00000521934, ENST00000522055, ENST00000522794, ENST00000523127, ENST00000523761, ENST00000545648, ENST00000871244, ENST00000871246, ENST00000937395, ENST00000937396

RefSeq mRNA: 2 — MANE Select: NM_016127 NM_001284239, NM_016127

CCDS: CCDS6074, CCDS64866

Canonical transcript exons

ENST00000256255 — 6 exons

Exon	Start	End
ENSE00001283091	30082847	30083064
ENSE00003467899	30065988	30066139
ENSE00003518811	30066777	30066918
ENSE00003627471	30069642	30070059
ENSE00003654510	30073877	30074055
ENSE00003890830	30063003	30063913

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 201.7024 / max 2992.5934, expressed in 1825 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92600	167.9690	1825
92602	9.4927	1750
92599	6.5789	1507
92601	6.3410	1667
92598	5.9650	1635
92589	1.2012	595
92588	1.2000	568
92587	0.9178	426
92586	0.7086	334
92597	0.5803	151

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.82	gold quality
endothelial cell	CL:0000115	99.77	gold quality
corpus epididymis	UBERON:0004359	99.71	gold quality
sperm	CL:0000019	99.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.69	gold quality
bronchial epithelial cell	CL:0002328	99.66	gold quality
epithelium of nasopharynx	UBERON:0001951	99.60	gold quality
substantia nigra pars compacta	UBERON:0001965	99.59	gold quality
nasopharynx	UBERON:0001728	99.58	gold quality
caput epididymis	UBERON:0004358	99.57	gold quality
superior vestibular nucleus	UBERON:0007227	99.57	gold quality
visceral pleura	UBERON:0002401	99.54	gold quality
male germ cell	CL:0000015	99.51	gold quality
pons	UBERON:0000988	99.51	gold quality
palpebral conjunctiva	UBERON:0001812	99.50	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.48	gold quality
middle temporal gyrus	UBERON:0002771	99.48	gold quality
pleura	UBERON:0000977	99.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.46	gold quality
prefrontal cortex	UBERON:0000451	99.44	gold quality
seminal vesicle	UBERON:0000998	99.44	gold quality
parietal pleura	UBERON:0002400	99.44	gold quality
islet of Langerhans	UBERON:0000006	99.43	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.43	gold quality
pigmented layer of retina	UBERON:0001782	99.39	gold quality
choroid plexus epithelium	UBERON:0003911	99.39	gold quality
epithelium of bronchus	UBERON:0002031	99.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.38	gold quality
lateral globus pallidus	UBERON:0002476	99.37	gold quality
retina	UBERON:0000966	99.36	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	3658.62
E-MTAB-8142	yes	3127.31
E-CURD-88	yes	2938.32
E-MTAB-6678	yes	2825.06
E-CURD-122	yes	2416.98
E-GEOD-111727	yes	2012.18
E-MTAB-9467	yes	1796.62
E-GEOD-135922	yes	1617.86
E-HCAD-8	yes	1460.29
E-HCAD-1	yes	114.55
E-MTAB-6701	yes	95.20
E-CURD-46	yes	51.57
E-HCAD-35	yes	41.09
E-MTAB-8410	yes	39.76
E-HCAD-10	yes	25.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting SARAF, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-4311	99.31	70.47	3041

Literature-anchored findings (GeneRIF, showing 18)

• Study shows that SARAF is an endoplasmic reticulum resident protein, which responds to cytosolic Ca2+ elevation after ER Ca2+ refilling by promoting a slow inactivation process of STIM2-dependent basal SOCE activity, as well as STIM1-mediated SOCE activity. (PMID:22464749)
• Store-operated Ca2+ entry is remodelled and controls in vitro angiogenesis in endothelial progenitor cells isolated from tumoral patients. (PMID:23049731)
• Deletion of STIM1(448-490) and, in particular, STIM1(447-460) and STIM1(475-490) markedly enhances interaction of SARAF with STIM1. (PMID:23816623)
• SARAF is constitutively expressed in the plasma membrane and interacts with Orai1. (PMID:26817842)
• SARAF overexpression attenuated store operated Ca2+ entry and the STIM1-Orai1 interaction in cells endogenously expressing STIM1 and Orai1 while RNAi-mediated SARAF silencing induced opposite effects. (PMID:27068144)
• These findings suggest that the surface location of SARAF is dependent on the expression of STIM1 in the plasma membrane. (PMID:27414851)
• SARAF modulates TRPC1, but not TRPC6, channel function in a STIM1-independent manner (PMID:27506849)
• This activation was sensitive to Src kinase inhibition, but not to CAMKII nor PKC inhibition, a result that sets STIM1 and SOCE as downstream targets of the axis Src-Raf-MEK-ERK, rather than upstream regulators. (PMID:28866365)
• SARAF also interacts with Orai1 and TRPC1 in cells endogenously expressing STIM1 and cells with a low STIM1 expression and modulates channel function. This review focuses on the modulation by SARAF of SOCE and other forms of Ca(2+) influx mediated by Orai1 and TRPC1 in order to provide spatio-temporally regulated Ca(2+) signals. (PMID:29223474)
• EFHB is a new store-operated Ca2+ entry regulator that modulates STIM1-SARAF interaction. (PMID:30481768)
• Y316F mutation altered the pattern of interaction between STIM1 and SARAF under resting conditions and upon Ca(2+) store depletion. Expression of the STIM1 Y316F mutant enhanced slow Ca(2+)-dependent inactivation (SCDI) as compared to STIM1 WT, an effect that was abolished by SARAF knockdown. (PMID:30975919)
• Described is the X-ray crystal structure of the SARAF luminal domain, SARAFL. This domain forms a novel 10-stranded beta-sandwich fold that includes a set of three conserved disulfide bonds, denoted the “SARAF-fold.” The structure reveals a domain-swapped dimer in which the last two beta-strands (beta9 and beta10) are exchanged forming a region denoted the “SARAF luminal switch” that is essential for dimerization. (PMID:31082439)
• Study shows that SARAF interacted with STIM1 to limit Ca2+ influx during physiological stimulation, but interaction of SARAF with STIM1 was transient during pathological stimulation of acinar cells, resulting in sustained, toxic Ca2+ influx. Transgenic expression of SARAF in mouse pancreatic acini reduced pathologic Ca2+ influx, prevented inflammation, and reduced tissue damage in mouse models of severe pancreatitis. (PMID:31493399)
• Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated Ca(2+) entry-mediated turnover of focal adhesions. (PMID:32079527)
• Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment. (PMID:32394484)
• Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF. (PMID:34705029)
• Reduced Ca[2+] mobilization in neonatal human platelets involves SARAF and pannexin-1. (PMID:38073055)
• MiR-30a-5p isoform -1|1 promotes the progression of gastric cancer by inhibiting TMEM66 and reducing intratumoral cytotoxic T cells. (PMID:38802035)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	saraf	ENSDARG00000070452
mus_musculus	Saraf	ENSMUSG00000031532
rattus_norvegicus	Saraf	ENSRNOG00000012329
caenorhabditis_elegans		WBGENE00011529

Protein

Protein identifiers

Store-operated calcium entry-associated regulatory factor — Q96BY9 (reviewed: Q96BY9)

Alternative names: HBV X-transactivated gene 3 protein, HBV XAg-transactivated protein 3, Protein FOAP-7, Transmembrane protein 66

All UniProt accessions (10): A0A140VK59, E5RFJ9, E5RHW0, E5RJG8, E5RJV6, Q96BY9, E5RK07, H0YAN9, H0YAZ1, H0YBH7

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions.

Subunit / interactions. Interacts with STIM1; the interaction is inhibited by the interaction of STIM1 with EFHB.

Subcellular location. Endoplasmic reticulum membrane Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in macrophages.

Domain organisation. The cytoplasmic C-terminal region mediates interaction with STIM1, while the N-terminal lumenal region mediates regulation of SOCE activity.

Similarity. Belongs to the SARAF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96BY9-1	1	yes
Q96BY9-2	2, Short

RefSeq proteins (2): NP_001271168, NP_057211* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009567	SARAF	Family

Pfam: PF06682

UniProt features (30 total): strand 12, sequence conflict 5, helix 2, topological domain 2, signal peptide 1, chain 1, turn 1, transmembrane region 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6O2V	X-RAY DIFFRACTION	1.58
6O2U	X-RAY DIFFRACTION	1.8
6O2W	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BY9-F1	68.55	0.39

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
148	dominant-negative mutant; leading to impair inhibition of soce.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 295 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MODULE_255, MODULE_317, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, CREBP1_Q2, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, E4F1_Q6, DOUGLAS_BMI1_TARGETS_DN, chr8p12, FOXJ2_02

GO Biological Process (3): calcium ion transport (GO:0006816), regulation of store-operated calcium entry (GO:2001256), monoatomic ion transport (GO:0006811)

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

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-plasma membrane contact site (GO:0140268), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion transport	1
store-operated calcium entry	1
regulation of calcium ion transport	1
transport	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
organelle membrane contact site	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SARAF	STIM1	Q13586	889
SARAF	TRPC1	P48995	805
SARAF	STIMATE	Q86TL2	781
SARAF	CRACR2A	Q9BSW2	745
SARAF	SLC35G1	Q2M3R5	727
SARAF	EFHB	Q8N7U6	718
SARAF	ORAI1	Q96D31	683
SARAF	ASPH	Q12797	670
SARAF	ORAI3	Q9BRQ5	631
SARAF	STIM2	Q9P246	630
SARAF	ESYT1	Q9BSJ8	599
SARAF	ORAI2	Q96SN7	552
SARAF	ESYT3	A0FGR9	532
SARAF	ERLEC1	Q96DZ1	506
SARAF	OS9	Q13438	480

IntAct

104 interactions, top by confidence:

A	B	Type	Score
ORAI1	STIM1	psi-mi:“MI:2364”(proximity)	0.960
SARAF	ITCH	psi-mi:“MI:0914”(association)	0.670
SARAF	ITCH	psi-mi:“MI:0915”(physical association)	0.670
STIM1	SARAF	psi-mi:“MI:0915”(physical association)	0.660
STIM1	SARAF	psi-mi:“MI:0403”(colocalization)	0.660
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3B1	psi-mi:“MI:0914”(association)	0.530
IL9R	RETSAT	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
ABHD5	ZPR1	psi-mi:“MI:0914”(association)	0.530
SLC22A15	ZFPL1	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530
STIM1	EFHB	psi-mi:“MI:0914”(association)	0.500
MBTPS2	SARAF	psi-mi:“MI:0915”(physical association)	0.400
ORAI1	SARAF	psi-mi:“MI:0403”(colocalization)	0.380
SARAF	HTR4	psi-mi:“MI:0915”(physical association)	0.370
RIR2	SARAF	psi-mi:“MI:0915”(physical association)	0.370
FCN1	SARAF	psi-mi:“MI:0915”(physical association)	0.370
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
Spast		psi-mi:“MI:0914”(association)	0.350
Vps4b	CNOT1	psi-mi:“MI:0914”(association)	0.350
CHMP4B	ELOC	psi-mi:“MI:0914”(association)	0.350
TMEM63B	CAV1	psi-mi:“MI:0914”(association)	0.350

BioGRID (252): SARAF (Affinity Capture-RNA), SARAF (Affinity Capture-RNA), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS), SARAF (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3P7X4, A1A4M2, A4IG66, A5D8P8, A7S641, A9SY65, F7C1E2, L7VG99, O75787, O94876, P0C204, P45433, P70302, P84903, Q08E24, Q13586, Q1KKT4, Q28DG6, Q3SZL5, Q3TAS6, Q3ZC50, Q58CP9, Q5R491, Q5R563, Q5R991, Q5RCI4, Q5TC12, Q5TYV0, Q5U2X6, Q5UCC4, Q5XI31, Q66I12, Q69ZZ6, Q6AYH6, Q6AYN2, Q6AZI2, Q6P606, Q6P7K5, Q6PD26, Q80U56

Diamond homologs: F1QPC3, F7C1E2, Q08E24, Q0IHF9, Q54P59, Q5R491, Q6AYN2, Q8R3Q0, Q96BY9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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
Vif-mediated degradation of APOBEC3G	5	16.3×	2e-03
Degradation of GLI1 by the proteasome	5	14.3×	3e-03
Defective CFTR causes cystic fibrosis	5	14.1×	3e-03
Asymmetric localization of PCP proteins	5	13.1×	3e-03
Activation of NF-kappaB in B cells	5	12.6×	3e-03
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	5	12.6×	3e-03
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	12.4×	3e-03
Regulation of PTEN stability and activity	5	11.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
transport across blood-brain barrier	7	11.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1006 predictions. Top by Δscore:

Variant	Effect	Δscore
8:30063910:TATC:T	acceptor_gain	1.0000
8:30066136:CGCT:C	acceptor_gain	1.0000
8:30066138:CT:C	acceptor_gain	1.0000
8:30066140:C:CC	acceptor_gain	1.0000
8:30066141:T:C	acceptor_gain	1.0000
8:30066142:T:C	acceptor_gain	1.0000
8:30066142:T:TC	acceptor_gain	1.0000
8:30066918:CCT:C	acceptor_gain	1.0000
8:30066919:CTTA:C	acceptor_loss	1.0000
8:30066920:T:C	acceptor_gain	1.0000
8:30069658:AAAG:A	donor_gain	1.0000
8:30070055:TCCCA:T	acceptor_gain	1.0000
8:30070056:CCCA:C	acceptor_gain	1.0000
8:30070056:CCCAC:C	acceptor_gain	1.0000
8:30070057:CCA:C	acceptor_gain	1.0000
8:30070057:CCAC:C	acceptor_gain	1.0000
8:30070058:CA:C	acceptor_gain	1.0000
8:30070058:CAC:C	acceptor_gain	1.0000
8:30070060:C:CC	acceptor_gain	1.0000
8:30063909:ATATC:A	acceptor_gain	0.9900
8:30063911:ATC:A	acceptor_gain	0.9900
8:30063911:ATCC:A	acceptor_loss	0.9900
8:30063912:TC:T	acceptor_gain	0.9900
8:30063913:CC:C	acceptor_gain	0.9900
8:30063914:C:CC	acceptor_gain	0.9900
8:30063915:T:C	acceptor_loss	0.9900
8:30065982:TCTTA:T	donor_loss	0.9900
8:30065983:CTTAC:C	donor_loss	0.9900
8:30065984:TTA:T	donor_loss	0.9900
8:30065985:TACCT:T	donor_loss	0.9900

AlphaMissense

2156 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:30070057:C:A	W95C	1.000
8:30070057:C:G	W95C	1.000
8:30070059:A:G	W95R	1.000
8:30070059:A:T	W95R	1.000
8:30070001:C:G	C114S	0.999
8:30070002:A:T	C114S	0.999
8:30070052:C:G	C97S	0.999
8:30070053:A:T	C97S	0.999
8:30073911:C:G	C83S	0.999
8:30073912:A:T	C83S	0.999
8:30069953:C:G	C130S	0.998
8:30069954:A:T	C130S	0.998
8:30070001:C:T	C114Y	0.998
8:30070051:A:C	C97W	0.998
8:30070053:A:G	C97R	0.998
8:30070058:C:G	W95S	0.998
8:30073912:A:G	C83R	0.998
8:30066810:C:T	G270D	0.997
8:30069942:A:C	Y134D	0.997
8:30069953:C:T	C130Y	0.997
8:30070000:A:C	C114W	0.997
8:30070002:A:G	C114R	0.997
8:30073910:A:C	C83W	0.997
8:30069941:T:G	Y134S	0.996
8:30069957:A:G	S129P	0.996
8:30070001:C:A	C114F	0.996
8:30070052:C:T	C97Y	0.996
8:30073962:C:G	C66S	0.996
8:30073963:A:T	C66S	0.996
8:30069954:A:G	C130R	0.995

dbSNP variants (sampled 300 via entrez): RS1000029301 (8:30082444 C>A,T), RS1000228929 (8:30065716 G>C), RS1000364795 (8:30083663 T>C), RS1000437004 (8:30083354 T>G), RS1000524846 (8:30074322 C>T), RS1000700751 (8:30079242 A>T), RS1000771459 (8:30085013 T>C), RS1000999353 (8:30078965 T>C), RS1001035663 (8:30072096 C>T), RS1001284313 (8:30078720 A>G), RS1001443148 (8:30082412 T>C,G), RS1001568702 (8:30078730 A>G), RS1001665235 (8:30075982 A>G,T), RS1001720199 (8:30069329 G>A), RS1001833539 (8:30072816 T>C)

Disease associations

OMIM: gene MIM:614768 | 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: yes

ChEMBL targets (1): CHEMBL6067396 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.83	Kd	147.2	nM	CHEMBL5653589
6.81	ED50	153.5	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149341: Binding affinity to human SARAF incubated for 45 mins by Kinobead based pull down assay	kd	0.1472	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	affects expression	1
corosolic acid	increases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzene	decreases expression	1
Cytarabine	decreases expression	1
Bucladesine	increases expression, affects cotreatment	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lead	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652383	Binding	Binding affinity to human SARAF incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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