SH2D5

Summary

SH2D5 (SH2 domain containing 5, HGNC:28819) is a protein-coding gene on chromosome 1p36.12, encoding SH2 domain-containing protein 5 (Q6ZV89). May be involved in synaptic plasticity regulation through the control of Rac-GTP levels.

Predicted to be located in synapse. Predicted to be active in postsynaptic density.

Source: NCBI Gene 400745 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_001103161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28819
Approved symbol	SH2D5
Name	SH2 domain containing 5
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189410
Ensembl biotype	protein_coding
Entrez	400745

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375031, ENST00000444387, ENST00000447746, ENST00000460804, ENST00000517430, ENST00000518294, ENST00000519434, ENST00000870131, ENST00000870132, ENST00000870133, ENST00000870134, ENST00000870135, ENST00000922380, ENST00000922381, ENST00000922382, ENST00000922383, ENST00000922384, ENST00000969600, ENST00000969601, ENST00000969602, ENST00000969603, ENST00000969604, ENST00000969605

RefSeq mRNA: 2 — MANE Select: NM_001103161 NM_001103160, NM_001103161

CCDS: CCDS41280, CCDS44080

Canonical transcript exons

ENST00000444387 — 10 exons

Exon	Start	End
ENSE00001391715	20724396	20724635
ENSE00001650743	20719731	20721995
ENSE00002130118	20732181	20732703
ENSE00002288621	20727958	20728086
ENSE00003538657	20723626	20723734
ENSE00003556081	20727523	20727603
ENSE00003583351	20725920	20726066
ENSE00003608020	20724083	20724251
ENSE00003642501	20727001	20727075
ENSE00003690103	20722756	20722915

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 91.83.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8298 / max 22.6247, expressed in 362 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10781	0.6803	338
10780	0.1125	55
10782	0.0370	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	91.83	gold quality
middle temporal gyrus	UBERON:0002771	90.91	gold quality
right frontal lobe	UBERON:0002810	90.80	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.80	gold quality
caudate nucleus	UBERON:0001873	89.03	gold quality
endothelial cell	CL:0000115	88.78	gold quality
anterior cingulate cortex	UBERON:0009835	88.71	gold quality
prefrontal cortex	UBERON:0000451	88.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.56	gold quality
frontal cortex	UBERON:0001870	88.32	gold quality
putamen	UBERON:0001874	88.25	gold quality
superior frontal gyrus	UBERON:0002661	88.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.75	gold quality
neocortex	UBERON:0001950	86.82	gold quality
cerebral cortex	UBERON:0000956	85.42	gold quality
postcentral gyrus	UBERON:0002581	85.37	gold quality
primary visual cortex	UBERON:0002436	84.44	gold quality
entorhinal cortex	UBERON:0002728	84.32	gold quality
parietal lobe	UBERON:0001872	83.21	gold quality
temporal lobe	UBERON:0001871	82.30	gold quality
forebrain	UBERON:0001890	81.92	gold quality
amygdala	UBERON:0001876	81.61	gold quality
hypothalamus	UBERON:0001898	80.61	gold quality
Ammon’s horn	UBERON:0001954	80.47	gold quality
occipital lobe	UBERON:0002021	80.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.07	gold quality
brain	UBERON:0000955	78.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.57	silver quality
Brodmann (1909) area 46	UBERON:0006483	77.08	silver quality
left testis	UBERON:0004533	76.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting SH2D5, 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-4283	100.00	66.42	2097
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4687-3P	99.48	66.41	968

Literature-anchored findings (GeneRIF, showing 2)

• results suggest that SH2D5 is an HBV-induced protein capable of binding to TKT, leading to induction of HCC cell proliferation. (PMID:30659097)
• Prognostic significance of SH2D5 expression in lung adenocarcinoma and its relation to immune cell infiltration. (PMID:37187527)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sh2d5	ENSMUSG00000045349
rattus_norvegicus	Sh2d5	ENSRNOG00000014909
drosophila_melanogaster	dock	FBGN0010583
caenorhabditis_elegans		WBGENE00006410

Paralogs (9): DAPP1 (ENSG00000070190), NCK2 (ENSG00000071051), GRAP2 (ENSG00000100351), SLA2 (ENSG00000101082), GRAP (ENSG00000154016), SLA (ENSG00000155926), NCK1 (ENSG00000158092), GRB2 (ENSG00000177885), GRAPL (ENSG00000189152)

Protein

Protein identifiers

SH2 domain-containing protein 5 — Q6ZV89 (reviewed: Q6ZV89)

All UniProt accessions (5): E5RGJ3, E5RGV2, E5RJW5, J3KQT6, Q6ZV89

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in synaptic plasticity regulation through the control of Rac-GTP levels.

Subunit / interactions. Interacts with BCR.

Subcellular location. Postsynaptic density.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZV89-1	1	yes
Q6ZV89-2	2

RefSeq proteins (2): NP_001096630, NP_001096631* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily

UniProt features (5 total): domain 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZV89-F1	71.38	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, BILD_HRAS_ONCOGENIC_SIGNATURE, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOCC_POSTSYNAPSE, GOCC_SYNAPSE, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, chr1p36, MARTENS_TRETINOIN_RESPONSE_UP, FORTSCHEGGER_PHF8_TARGETS_DN, LIM_MAMMARY_STEM_CELL_UP, GOCC_NEURON_TO_NEURON_SYNAPSE, CAHOY_NEURONAL, BREDEMEYER_RAG_SIGNALING_VIA_ATM_NOT_VIA_NFKB_UP, GSE5503_MLN_DC_VS_PLN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, GSE5503_MLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_UP

GO Biological Process (0):

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

GO Cellular Component (2): postsynaptic density (GO:0014069), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
asymmetric synapse	1
postsynaptic specialization	1
cell junction	1

Protein interactions and networks

STRING

284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH2D5	BCR	P11274	606
SH2D5	TKT	P29401	560
SH2D5	TKTL2	Q9H0I9	538
SH2D5	TKTL1	P51854	528
SH2D5	CTXN1	P60606	501
SH2D5	ZNF234	Q14588	479
SH2D5	FRRS1L	Q9P0K9	457
SH2D5	SPOCD1	Q6ZMY3	456
SH2D5	ARHGAP22	Q7Z5H3	406
SH2D5	RGS19	P49795	396
SH2D5	OLFML1	Q6UWY5	394
SH2D5	BEND6	Q5SZJ8	392
SH2D5	TTC9	Q92623	386
SH2D5	EVI2A	P22794	383
SH2D5	CASKIN2	Q8WXE0	376

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PDZK1P1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
BCR	CNOT1	psi-mi:“MI:0914”(association)	0.350
PDZK1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
RDX	RNF113A	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): SH2D5 (Affinity Capture-MS), SH2D5 (Affinity Capture-MS), SH2D5 (Affinity Capture-MS), SH2D5 (Affinity Capture-MS), SH2D5 (Affinity Capture-MS), SH2D5 (Affinity Capture-MS), SH2D5 (Protein-peptide)

ESM2 similar proteins: A1YGK1, A2T7E6, A4D1S0, A6NGW2, F2YMG0, H7C350, O15533, O43593, O60304, O70146, O94761, P0CW18, P27106, P59942, P79295, Q15569, Q1JPB9, Q2TBC4, Q3UM83, Q4TUC0, Q5DRQ5, Q5M844, Q5R732, Q5TJE4, Q63572, Q6P0A1, Q6PZD2, Q6ZV89, Q75NR7, Q7RTU9, Q7Z6P3, Q866Y3, Q8BLH5, Q8BWG4, Q8JZW5, Q8N4L8, Q8NBB4, Q8QZY4, Q8TER5, Q8VIM6

Diamond homologs: Q5R732, Q6ZV89, Q8JZW5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1982 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20721996:C:CC	acceptor_gain	1.0000
1:20722750:TCTTA:T	donor_loss	1.0000
1:20722751:CTTAC:C	donor_loss	1.0000
1:20722752:TTA:T	donor_loss	1.0000
1:20722753:TACC:T	donor_loss	1.0000
1:20722755:C:A	donor_loss	1.0000
1:20722911:AGGGC:A	acceptor_gain	1.0000
1:20722912:GGGC:G	acceptor_gain	1.0000
1:20722913:GGC:G	acceptor_gain	1.0000
1:20722914:GC:G	acceptor_gain	1.0000
1:20722914:GCCTA:G	acceptor_loss	1.0000
1:20722915:CC:C	acceptor_gain	1.0000
1:20722915:CCT:C	acceptor_loss	1.0000
1:20722916:C:CC	acceptor_gain	1.0000
1:20722916:CTAG:C	acceptor_loss	1.0000
1:20722917:T:G	acceptor_loss	1.0000
1:20722923:C:CT	acceptor_gain	1.0000
1:20723620:TCCTA:T	donor_loss	1.0000
1:20723621:CCTAC:C	donor_loss	1.0000
1:20723622:CTAC:C	donor_loss	1.0000
1:20723623:TACCT:T	donor_loss	1.0000
1:20723624:A:T	donor_loss	1.0000
1:20723625:C:A	donor_loss	1.0000
1:20723735:C:CC	acceptor_gain	1.0000
1:20724395:CCCCA:C	donor_gain	1.0000
1:20724632:GGAC:G	acceptor_loss	1.0000
1:20724634:ACC:A	acceptor_loss	1.0000
1:20724636:CTGGG:C	acceptor_loss	1.0000
1:20725923:T:A	donor_gain	1.0000
1:20727613:A:T	acceptor_gain	1.0000

AlphaMissense

2701 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20724176:G:T	R236S	0.997
1:20724163:A:T	I240N	0.995
1:20724171:C:A	K237N	0.995
1:20724171:C:G	K237N	0.995
1:20724163:A:G	I240T	0.994
1:20724161:G:T	R241S	0.991
1:20724163:A:C	I240S	0.990
1:20727041:A:G	F68S	0.990
1:20724153:C:A	K243N	0.989
1:20724153:C:G	K243N	0.989
1:20722870:G:C	F318L	0.988
1:20722870:G:T	F318L	0.988
1:20722872:A:G	F318L	0.988
1:20727603:A:G	Y30H	0.987
1:20725942:A:G	F123S	0.986
1:20727053:A:T	V64D	0.986
1:20724173:T:C	K237E	0.985
1:20725993:A:G	F106S	0.985
1:20724139:C:T	G248E	0.983
1:20724166:G:T	A239D	0.983
1:20724175:C:G	R236P	0.982
1:20725949:G:C	H121D	0.982
1:20722790:A:T	V345D	0.980
1:20727040:G:C	F68L	0.980
1:20727040:G:T	F68L	0.980
1:20727042:A:G	F68L	0.980
1:20721978:G:C	F362L	0.979
1:20721978:G:T	F362L	0.979
1:20721980:A:G	F362L	0.979
1:20724607:C:G	R140P	0.979

dbSNP variants (sampled 300 via entrez): RS1000069532 (1:20731308 A>C,G), RS1000131132 (1:20731232 T>G), RS1000184567 (1:20724033 C>CGG), RS1000236633 (1:20726166 C>A,T), RS1000294533 (1:20731646 T>A,G), RS1000324119 (1:20721121 G>A), RS1000803647 (1:20720074 C>T), RS1000837765 (1:20726383 C>T), RS1001128090 (1:20729314 C>T), RS1001401842 (1:20726425 T>C), RS1001477818 (1:20729663 C>A,T), RS1001545672 (1:20721517 C>G,T), RS1002012990 (1:20726150 C>G,T), RS1002192337 (1:20730023 C>T), RS1002392025 (1:20730345 G>T)

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)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10916852	Efficacy	3	gemcitabine	Pancreatic Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10916852	SH2D5	3	1.75	1	gemcitabine

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression	2
beta-Naphthoflavone	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
bufotalin	increases expression	1
propionaldehyde	increases expression	1
sodium arsenate	increases abundance, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
diallyl trisulfide	increases expression	1
pentanal	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
ormosil	affects binding, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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