SH2D4B

Summary

SH2D4B (SH2 domain containing 4B, HGNC:31440) is a protein-coding gene on chromosome 10q23.1, encoding SH2 domain-containing protein 4B (Q5SQS7).

Predicted to be active in cytoplasm.

Source: NCBI Gene 387694 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_001388272

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31440
Approved symbol	SH2D4B
Name	SH2 domain containing 4B
Location	10q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178217
Ensembl biotype	protein_coding
Entrez	387694

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000313455, ENST00000339284, ENST00000372150, ENST00000481537, ENST00000646907

RefSeq mRNA: 3 — MANE Select: NM_001388272 NM_001145719, NM_001388272, NM_207372

CCDS: CCDS44449, CCDS7370, CCDS91286

Canonical transcript exons

ENST00000646907 — 8 exons

Exon	Start	End
ENSE00001380054	80603579	80603795
ENSE00001406519	80570154	80570316
ENSE00001418408	80537902	80538515
ENSE00001428908	80588630	80588777
ENSE00001431017	80571431	80571578
ENSE00003563757	80609424	80609551
ENSE00003826850	80634285	80634505
ENSE00003829705	80643993	80646560

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 92.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0071 / max 5.5722, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
205922	0.0071	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.83	gold quality
oocyte	CL:0000023	68.78	gold quality
cortical plate	UBERON:0005343	61.05	gold quality
buccal mucosa cell	CL:0002336	57.40	gold quality
ganglionic eminence	UBERON:0004023	56.21	gold quality
bone marrow cell	CL:0002092	51.44	gold quality
blood	UBERON:0000178	48.11	gold quality
prefrontal cortex	UBERON:0000451	47.06	gold quality
upper lobe of left lung	UBERON:0008952	47.04	gold quality
bone marrow	UBERON:0002371	46.46	gold quality
upper lobe of lung	UBERON:0008948	46.41	gold quality
right lung	UBERON:0002167	45.89	gold quality
colonic epithelium	UBERON:0000397	45.37	gold quality
lower esophagus mucosa	UBERON:0035834	45.31	silver quality
skin of hip	UBERON:0001554	44.50	silver quality
lung	UBERON:0002048	44.46	gold quality
granulocyte	CL:0000094	43.89	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
upper leg skin	UBERON:0004262	42.57	silver quality
testis	UBERON:0000473	42.45	gold quality
frontal cortex	UBERON:0001870	42.33	gold quality
placenta	UBERON:0001987	41.93	gold quality
left testis	UBERON:0004533	41.67	gold quality
neocortex	UBERON:0001950	41.66	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
tibial artery	UBERON:0007610	41.30	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	11.83
E-ANND-3	no	4.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

105 targeting SH2D4B, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-3180-5P	99.82	69.12	2422

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh2d4bb	ENSDARG00000015144
danio_rerio	sh2d4ba	ENSDARG00000069374
mus_musculus	Sh2d4b	ENSMUSG00000037833
rattus_norvegicus	Sh2d4b	ENSRNOG00000042623
caenorhabditis_elegans		WBGENE00008733

Paralogs (4): SH2D2A (ENSG00000027869), SH2D4A (ENSG00000104611), SH2D7 (ENSG00000183476), HSH2D (ENSG00000196684)

Protein

Protein identifiers

SH2 domain-containing protein 4B — Q5SQS7 (reviewed: Q5SQS7)

All UniProt accessions (2): Q5SQS7, A0A2R8Y5Q0

Isoforms (3)

UniProt ID	Names	Canonical?
Q5SQS7-1	1	yes
Q5SQS7-2	2
Q5SQS7-3	3

RefSeq proteins (3): NP_001139191, NP_001375201, NP_997255 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR035839	SH2D4B_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily

Pfam: PF00017

UniProt features (11 total): splice variant 4, sequence conflict 2, sequence variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SQS7-F1	83.87	0.59

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, chr10q23, YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, PAX7_TARGET_GENES, MIR3662, MIR3646, MIR5582_3P, MIR579_3P, MIR664B_3P, MIR7159_5P, MIR2053

GO Biological Process (0):

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH2D4B	DYDC1	Q8WWB3	686
SH2D4B	DYDC2	Q96IM9	645
SH2D4B	TSPAN14	Q8NG11	583
SH2D4B	UBOX5	O94941	535
SH2D4B	FBXO39	Q8N4B4	527
SH2D4B	LONP2	Q86WA8	478
SH2D4B	TMEM254	Q8TBM7	433
SH2D4B	RANGRF	Q9HD47	429
SH2D4B	EFCC1	Q9HA90	418
SH2D4B	FCHSD2	O94868	417
SH2D4B	SHQ1	Q6PI26	407
SH2D4B	CLRN2	A0PK11	401
SH2D4B	PDZRN3	Q9UPQ7	374
SH2D4B	PLAC9	Q5JTB6	370
SH2D4B	ANXA11	P50995	369

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SH2D4B	ALK	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): SH2D4B (Affinity Capture-RNA)

ESM2 similar proteins: A2AL36, A3KQ58, A4IFR8, A6NEE1, A6X942, B1WBU8, B2RPU2, E9Q9R9, E9QA62, O75335, P39880, P53564, P97434, Q08CX2, Q1RM35, Q2NKX9, Q2VUH7, Q32LH1, Q3TYL0, Q3UP38, Q4V817, Q5EB20, Q5SQS7, Q5SXA9, Q63312, Q6AYC8, Q6DRB1, Q6NXJ0, Q6PA69, Q6WCQ1, Q6Y7W8, Q76G19, Q7SYB5, Q7TNY6, Q80Y56, Q80Y83, Q8BMP6, Q8CJ96, Q8IX03, Q8TDM6

Diamond homologs: A6NKC9, A6X942, G5ECJ6, O08908, O88834, P03949, P46109, P47941, Q00655, Q08012, Q08CX2, Q56A36, Q5SQS7, Q5U2U2, Q6AYC8, Q6VYH9, Q6YKA8, Q8BI17, Q8UUU2, Q96JZ2, Q9D7V1, Q9H788, Q9NP31, Q9QXK9, P00519, P00520, P00521, P10447, P20936, P29353, P32577, P41239, P41240, P41241, P42684, P50904, P98083, Q03160, Q0IIE2, Q0VBZ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1778 predictions. Top by Δscore:

Variant	Effect	Δscore
10:80538511:GCGAG:G	donor_gain	1.0000
10:80538512:CGAG:C	donor_loss	1.0000
10:80538514:AG:A	donor_loss	1.0000
10:80538515:GGTA:G	donor_loss	1.0000
10:80570145:A:AG	acceptor_gain	1.0000
10:80570145:ATT:A	acceptor_gain	1.0000
10:80570146:T:G	acceptor_gain	1.0000
10:80570147:T:A	acceptor_gain	1.0000
10:80570300:G:GT	donor_gain	1.0000
10:80570300:G:T	donor_gain	1.0000
10:80570304:C:G	donor_gain	1.0000
10:80571425:T:A	acceptor_gain	1.0000
10:80571428:TA:T	acceptor_loss	1.0000
10:80571429:A:AG	acceptor_gain	1.0000
10:80571429:A:AT	acceptor_loss	1.0000
10:80571430:G:GG	acceptor_gain	1.0000
10:80571430:GGA:G	acceptor_gain	1.0000
10:80571570:G:GT	donor_gain	1.0000
10:80571574:TCAAG:T	donor_loss	1.0000
10:80571575:CAAGG:C	donor_loss	1.0000
10:80571576:AAGGT:A	donor_loss	1.0000
10:80571579:G:A	donor_loss	1.0000
10:80571580:T:G	donor_loss	1.0000
10:80576042:AT:A	acceptor_gain	1.0000
10:80576042:ATG:A	acceptor_gain	1.0000
10:80576042:ATGG:A	acceptor_gain	1.0000
10:80576042:ATGGG:A	acceptor_gain	1.0000
10:80588776:GT:G	donor_gain	1.0000
10:80603574:TCCA:T	acceptor_loss	1.0000
10:80603577:A:AG	acceptor_gain	1.0000

AlphaMissense

2849 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006326 (10:80573560 G>T), RS1000019902 (10:80592096 A>C), RS1000068690 (10:80596508 T>C), RS1000081878 (10:80586967 C>A,G,T), RS1000187285 (10:80614127 GGT>G), RS1000221263 (10:80608194 C>T), RS1000222066 (10:80616618 A>C), RS1000224760 (10:80613498 G>C), RS1000235505 (10:80642246 C>A), RS1000276868 (10:80575665 C>T), RS1000306809 (10:80571126 C>G), RS1000342802 (10:80582483 C>A,G,T), RS1000343399 (10:80556531 A>G,T), RS1000344097 (10:80607845 G>A), RS1000356551 (10:80582190 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

14 associations (top):

Study	Trait	p-value
GCST001368_16	Capecitabine sensitivity	7.000000e-06
GCST002817_23	Alzheimer’s disease in APOE e4- carriers	1.000000e-06
GCST003262_759	Post bronchodilator FEV1	3.000000e-06
GCST003262_760	Post bronchodilator FEV1	5.000000e-06
GCST003262_788	Post bronchodilator FEV1	1.000000e-06
GCST004131_69	Inflammatory bowel disease	5.000000e-08
GCST004132_36	Crohn’s disease	7.000000e-08
GCST004896_5	Overall survival in serous epithelial ovarian cancer treated with paclitaxel and cisplatin	8.000000e-07
GCST005834_5	Response to SSRI in MDD or openness	9.000000e-07
GCST006360_1	IgA levels	2.000000e-08
GCST009391_1018	Metabolite levels	7.000000e-06
GCST009391_2029	Metabolite levels	7.000000e-06
GCST012442_19	Age-related hearing impairment	8.000000e-11
GCST90002401_216	Platelet distribution width	8.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0000638	overall survival
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007914	openness measurement
EFO:0010360	lysophosphatidylcholine 18:1 measurement
EFO:0010371	lysophosphatidylethanolamine 22:6 measurement
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	decreases expression, affects cotreatment	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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