SHD

Summary

SHD (Src homology 2 domain containing transforming protein D, HGNC:30633) is a protein-coding gene on chromosome 19p13.3, encoding SH2 domain-containing adapter protein D (Q96IW2). May function as an adapter protein.

Predicted to enable phosphotyrosine residue binding activity.

Source: NCBI Gene 56961 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_020209

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30633
Approved symbol	SHD
Name	Src homology 2 domain containing transforming protein D
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105251
Ensembl biotype	protein_coding
OMIM	610481
Entrez	56961

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000543264, ENST00000593383, ENST00000597466, ENST00000599689, ENST00000600475, ENST00000953157, ENST00000953158, ENST00000953159, ENST00000953160, ENST00000953161

RefSeq mRNA: 2 — MANE Select: NM_020209 NM_001372011, NM_020209

CCDS: CCDS12125

Canonical transcript exons

ENST00000543264 — 6 exons

Exon	Start	End
ENSE00000664065	4282870	4282975
ENSE00000664066	4283054	4283242
ENSE00001052413	4279266	4280360
ENSE00002300634	4290447	4290722
ENSE00003488753	4288243	4288362
ENSE00003634481	4284781	4284904

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 94.35.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0256 / max 292.9757, expressed in 353 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173315	0.6261	166
173312	0.2371	94
173313	0.1634	69
173325	0.1556	72
173323	0.1517	56
173317	0.1056	37
173320	0.1004	36
173327	0.0950	45
173321	0.0758	36
173326	0.0725	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	94.35	gold quality
right atrium auricular region	UBERON:0006631	86.95	gold quality
cardiac atrium	UBERON:0002081	86.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.50	gold quality
right lobe of liver	UBERON:0001114	84.49	gold quality
oocyte	CL:0000023	84.40	gold quality
right frontal lobe	UBERON:0002810	83.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.16	gold quality
prefrontal cortex	UBERON:0000451	80.79	gold quality
ileal mucosa	UBERON:0000331	78.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.42	gold quality
frontal cortex	UBERON:0001870	77.98	gold quality
cardiac muscle of right atrium	UBERON:0003379	77.77	gold quality
anterior cingulate cortex	UBERON:0009835	77.57	gold quality
neocortex	UBERON:0001950	76.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.55	gold quality
cerebellar cortex	UBERON:0002129	76.27	gold quality
cerebellar hemisphere	UBERON:0002245	76.26	gold quality
primary visual cortex	UBERON:0002436	75.85	gold quality
left ventricle myocardium	UBERON:0006566	75.41	gold quality
hypothalamus	UBERON:0001898	75.34	gold quality
myocardium	UBERON:0002349	75.04	gold quality
cerebellum	UBERON:0002037	74.87	gold quality
rectum	UBERON:0001052	74.47	gold quality
cerebral cortex	UBERON:0000956	74.38	gold quality
amygdala	UBERON:0001876	74.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.76	gold quality
transverse colon	UBERON:0001157	73.74	gold quality
liver	UBERON:0002107	72.45	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	581.97
E-CURD-122	yes	13.82
E-MTAB-9067	yes	11.45
E-GEOD-93593	yes	4.23
E-HCAD-10	yes	3.85
E-ANND-3	yes	3.50

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	shdb	ENSDARG00000062109
danio_rerio	shda	ENSDARG00000094243
mus_musculus	Shd	ENSMUSG00000039154
rattus_norvegicus	Shd	ENSRNOG00000049983

Paralogs (3): SHB (ENSG00000107338), SHF (ENSG00000138606), SHE (ENSG00000169291)

Protein

Protein identifiers

SH2 domain-containing adapter protein D — Q96IW2 (reviewed: Q96IW2)

All UniProt accessions (3): Q96IW2, M0QYZ4, M0R1V9

UniProt curated annotations — full annotation on UniProt →

Function. May function as an adapter protein.

Post-translational modifications. Tyrosine phosphorylated by ABL.

RefSeq proteins (2): NP_001358940, NP_064594* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR035046	SHD_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR051846	SH2_domain_adapters	Family

Pfam: PF00017

UniProt features (10 total): region of interest 3, compositionally biased region 2, sequence variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IW2-F1	66.88	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, chr19p13, GOMF_PHOSPHOPROTEIN_BINDING, GOMF_PROTEIN_PHOSPHORYLATED_AMINO_ACID_BINDING, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_12, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, GOMF_PHOSPHOTYROSINE_RESIDUE_BINDING, SUPT16H_TARGET_GENES, ZNF92_TARGET_GENES, KUMAR_TARGETS_OF_MLL_AF9_FUSION, GSE14350_IL2RB_KO_VS_WT_TREG_UP, GSE1448_CTRL_VS_ANTI_VALPHA2_DP_THYMOCYTE_UP, GSE15324_NAIVE_VS_ACTIVATED_CD8_TCELL_UP

GO Biological Process (0):

GO Molecular Function (2): phosphotyrosine residue binding (GO:0001784), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein phosphorylated amino acid binding	1
binding	1

Protein interactions and networks

STRING

216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHD	DHRS2	Q13268	766
SHD	SHE	Q5VZ18	443
SHD	SHC1	P29353	433
SHD	PAM	P19021	418
SHD	SH2D6	Q7Z4S9	359
SHD	POPDC3	Q9HBV1	320
SHD	STOML3	Q8TAV4	317
SHD	CIMIP2B	A8MTA8	311
SHD	LTK	P29376	307
SHD	NR0B2	Q15466	301
SHD	KDF1	Q8NAX2	299
SHD	TMEM52B	Q4KMG9	295
SHD	SBK2	P0C263	289
SHD	SYCN	Q0VAF6	273
SHD	MT-CO1	P00395	273

IntAct

19 interactions, top by confidence:

A	B	Type	Score
NCK2	SHD	psi-mi:“MI:0915”(physical association)	0.560
SHD	CAPN10	psi-mi:“MI:0915”(physical association)	0.490
PSG11	SHD	psi-mi:“MI:0915”(physical association)	0.490
SHD	MET	psi-mi:“MI:0407”(direct interaction)	0.440
SHD	OLIG1	psi-mi:“MI:0915”(physical association)	0.370
SHD	OSBPL6	psi-mi:“MI:0915”(physical association)	0.370
KRTCAP2	SHD	psi-mi:“MI:0915”(physical association)	0.370
BECN1	SHD	psi-mi:“MI:0915”(physical association)	0.370
SHD	MRPS22	psi-mi:“MI:0915”(physical association)	0.370
ALK	SHD	psi-mi:“MI:0915”(physical association)	0.370
	HLA-C	psi-mi:“MI:0914”(association)	0.350
SHD	MYH7	psi-mi:“MI:0914”(association)	0.350
TMOD4	FECH	psi-mi:“MI:0914”(association)	0.350
NCK2	SHD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): CAPN10 (Two-hybrid), PSG11 (Two-hybrid), KRTCAP2 (Two-hybrid), OLIG1 (Two-hybrid), OSBPL6 (Two-hybrid), BECN1 (Two-hybrid), MRPS22 (Two-hybrid), SHD (Two-hybrid), SHD (Reconstituted Complex), SHD (Reconstituted Complex), SHD (Reconstituted Complex), SHD (Reconstituted Complex), SHD (Reconstituted Complex), MYH8 (Affinity Capture-MS), MYH7 (Affinity Capture-MS)

ESM2 similar proteins: A2A7Y5, A2VE02, A5D7K1, A6NKC9, O43561, O54957, O70601, O88834, P14784, P15391, P16382, P24394, P25917, P25918, Q13651, Q13796, Q2NL68, Q38J84, Q38J85, Q3KP66, Q3LRP3, Q3SYS8, Q3U1F9, Q3UU41, Q58CT8, Q5BK39, Q5FVQ5, Q5JTC6, Q5SX79, Q64322, Q6RFH4, Q6WG24, Q7M4L6, Q7TN12, Q7Z591, Q863Z5, Q86WR7, Q8BHB3, Q8BI17, Q8C708

Diamond homologs: A6NKC9, A6X942, O88834, P00519, P00520, P00521, P10447, P20936, P29353, P32577, P41239, P41240, P41241, P42684, P50904, P98083, Q03160, Q08012, Q08CX2, Q0IIE2, Q0VBZ0, Q14451, Q15464, Q1RMW5, Q4JIM5, Q56A36, Q5SQS7, Q6AYC8, Q6PD21, Q6VYH9, Q6YKA8, Q8BI17, Q96IW2, Q96JZ2, Q9D7V1, Q9H788, Q9NP31, Q9QXK9, Q9QZC5, A6QLK6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1249 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4280358:G:GT	donor_gain	1.0000
19:4282865:C:CA	acceptor_gain	1.0000
19:4282865:CGCA:C	acceptor_loss	1.0000
19:4282866:GCA:G	acceptor_loss	1.0000
19:4282867:CA:C	acceptor_loss	1.0000
19:4282868:A:AC	acceptor_loss	1.0000
19:4282868:A:AG	acceptor_gain	1.0000
19:4282868:AGCT:A	acceptor_gain	1.0000
19:4282868:AGCTG:A	acceptor_gain	1.0000
19:4282869:G:GT	acceptor_gain	1.0000
19:4282869:GC:G	acceptor_gain	1.0000
19:4282869:GCT:G	acceptor_gain	1.0000
19:4282869:GCTG:G	acceptor_gain	1.0000
19:4282869:GCTGG:G	acceptor_gain	1.0000
19:4282965:GGTCA:G	donor_gain	1.0000
19:4282971:GAGTG:G	donor_gain	1.0000
19:4282973:GTG:G	donor_gain	1.0000
19:4282976:G:GG	donor_gain	1.0000
19:4282977:T:A	donor_loss	1.0000
19:4283049:CCTA:C	acceptor_loss	1.0000
19:4283050:CTA:C	acceptor_loss	1.0000
19:4283051:TAG:T	acceptor_loss	1.0000
19:4283052:A:AG	acceptor_gain	1.0000
19:4283052:A:T	acceptor_loss	1.0000
19:4283053:G:GG	acceptor_gain	1.0000
19:4283167:G:GT	donor_gain	1.0000
19:4283186:A:AG	donor_gain	1.0000
19:4283232:G:GT	donor_gain	1.0000
19:4284902:GCC:G	donor_gain	1.0000
19:4284905:G:GG	donor_gain	1.0000

AlphaMissense

2220 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4283203:T:A	W185R	0.999
19:4283203:T:C	W185R	0.999
19:4283205:G:C	W185C	0.999
19:4283205:G:T	W185C	0.999
19:4288244:T:A	W240R	0.998
19:4288244:T:C	W240R	0.998
19:4288310:T:G	Y262D	0.998
19:4288314:T:C	L263P	0.998
19:4283191:T:C	Y181H	0.997
19:4283209:T:A	W187R	0.997
19:4283209:T:C	W187R	0.997
19:4283211:G:C	W187C	0.997
19:4283211:G:T	W187C	0.997
19:4283225:T:C	I192T	0.996
19:4288353:T:C	L276S	0.996
19:4290548:T:A	V313D	0.996
19:4280163:T:G	Y34D	0.995
19:4280187:T:C	F42L	0.995
19:4280189:C:A	F42L	0.995
19:4280189:C:G	F42L	0.995
19:4283225:T:A	I192N	0.995
19:4288307:A:C	S261R	0.995
19:4288309:C:A	S261R	0.995
19:4288309:C:G	S261R	0.995
19:4288359:T:C	L278P	0.995
19:4283192:A:G	Y181C	0.994
19:4288310:T:A	Y262N	0.994
19:4290602:T:A	L331Q	0.994
19:4283192:A:C	Y181S	0.993
19:4283225:T:G	I192S	0.993

dbSNP variants (sampled 300 via entrez): RS1000116650 (19:4278176 A>G), RS1000326532 (19:4290945 G>A,C), RS1000791310 (19:4289267 C>A,T), RS1000823890 (19:4289955 A>G), RS1001028938 (19:4283581 T>G), RS1001162998 (19:4283916 G>A,C), RS1001340069 (19:4283482 C>T), RS1001461322 (19:4283814 G>A), RS1001475729 (19:4286483 G>A,C,T), RS1001506706 (19:4286715 T>C), RS1001704524 (19:4281133 G>A), RS1001805526 (19:4279346 C>T), RS1002062528 (19:4282708 T>A), RS1002415225 (19:4280260 C>T), RS1002433136 (19:4282507 C>T)

Disease associations

OMIM: gene MIM:610481 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011800_11	Post-bronchodilator lung function in asthma (FVC)	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Doxorubicin	decreases expression, affects expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
butyraldehyde	increases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Cisplatin	affects expression	1
Copper	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
N-Nitrosopyrrolidine	decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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