SRPRA

Summary

SRPRA (SRP receptor subunit alpha, HGNC:11307) is a protein-coding gene on chromosome 11q24.2, encoding Signal recognition particle receptor subunit alpha (P08240). Component of the signal recognition particle (SRP) complex receptor (SR). It is a selective cancer dependency (DepMap: 77.4% of cell lines).

The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6734 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Shwachman-Diamond syndrome (Moderate, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 41 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 77.4% of screened cell lines
• MANE Select transcript: NM_003139

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11307
Approved symbol	SRPRA
Name	SRP receptor subunit alpha
Location	11q24.2
Locus type	gene with protein product
Status	Approved
Aliases	SRP-alpha, Sralpha, SR-alpha
Ensembl gene	ENSG00000182934
Ensembl biotype	protein_coding
OMIM	182180
Entrez	6734

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000332118, ENST00000527817, ENST00000528744, ENST00000530680, ENST00000531104, ENST00000532259, ENST00000532268, ENST00000891649, ENST00000891650, ENST00000942969

RefSeq mRNA: 2 — MANE Select: NM_003139 NM_001177842, NM_003139

CCDS: CCDS31717, CCDS53722

Canonical transcript exons

ENST00000332118 — 14 exons

Exon	Start	End
ENSE00001299168	126267549	126267712
ENSE00001465000	126262938	126264044
ENSE00001465001	126264191	126264289
ENSE00001465002	126264376	126264539
ENSE00001465004	126264959	126265172
ENSE00001465008	126266187	126266278
ENSE00001465009	126266476	126266629
ENSE00001465010	126266763	126266922
ENSE00001506987	126267175	126267335
ENSE00002174793	126268688	126268895
ENSE00003472077	126268003	126268086
ENSE00003554278	126265268	126265440
ENSE00003561393	126265963	126266081
ENSE00003585395	126265737	126265823

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.2551 / max 514.5296, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123021	78.1400	1826
123022	3.1151	1601

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.41	gold quality
body of pancreas	UBERON:0001150	99.13	gold quality
type B pancreatic cell	CL:0000169	98.89	gold quality
islet of Langerhans	UBERON:0000006	98.58	gold quality
pancreas	UBERON:0001264	98.48	gold quality
adenohypophysis	UBERON:0002196	98.11	gold quality
pituitary gland	UBERON:0000007	98.05	gold quality
stromal cell of endometrium	CL:0002255	98.03	gold quality
saliva-secreting gland	UBERON:0001044	98.02	gold quality
corpus epididymis	UBERON:0004359	97.96	gold quality
body of stomach	UBERON:0001161	97.95	gold quality
cartilage tissue	UBERON:0002418	97.91	gold quality
right lobe of liver	UBERON:0001114	97.88	gold quality
minor salivary gland	UBERON:0001830	97.73	gold quality
left uterine tube	UBERON:0001303	97.54	gold quality
left lobe of thyroid gland	UBERON:0001120	97.51	gold quality
right lobe of thyroid gland	UBERON:0001119	97.46	gold quality
gall bladder	UBERON:0002110	97.31	gold quality
upper lobe of left lung	UBERON:0008952	97.28	gold quality
endocervix	UBERON:0000458	97.24	gold quality
upper lobe of lung	UBERON:0008948	97.24	gold quality
left adrenal gland	UBERON:0001234	97.21	gold quality
thyroid gland	UBERON:0002046	97.21	gold quality
mouth mucosa	UBERON:0003729	97.18	gold quality
stomach	UBERON:0000945	97.17	gold quality
rectum	UBERON:0001052	97.16	gold quality
left adrenal gland cortex	UBERON:0035825	97.15	gold quality
liver	UBERON:0002107	97.14	gold quality
mucosa of stomach	UBERON:0001199	97.10	gold quality
right adrenal gland cortex	UBERON:0035827	97.09	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	6.84
E-MTAB-6379	no	764.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, TSC22D1

miRNA regulators (miRDB)

105 targeting SRPRA, 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-4481	100.00	66.42	1669
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 77.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Human genetic defects in SRP19 and SRPRA cause severe congenital neutropenia with distinctive proteome changes. (PMID:36223592)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	srpra	ENSDARG00000061124
mus_musculus	Srpra	ENSMUSG00000032042
rattus_norvegicus	Srpra	ENSRNOG00000010543
drosophila_melanogaster	SrpRalpha	FBGN0010391
caenorhabditis_elegans		WBGENE00009521

Paralogs (1): SRP54 (ENSG00000100883)

Protein

Protein identifiers

Signal recognition particle receptor subunit alpha — P08240 (reviewed: P08240)

Alternative names: Docking protein alpha

All UniProt accessions (1): P08240

UniProt curated annotations — full annotation on UniProt →

Function. Component of the signal recognition particle (SRP) complex receptor (SR). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system. Forms a guanosine 5’-triphosphate (GTP)-dependent complex with the SRP subunit SRP54. SRP receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER.

Subunit / interactions. Heterodimer with SRPRB. Interacts with the signal recognition particle (SRP) complex subunit SRP54. (Microbial infection) May interact with Zika virus strain Mr-766 non-structural protein 4A/NS4A. May interact with Zika virus French Polynesia 10087PF/2013 non-structural protein 4A/NS4A. (Microbial infection) May interact with Dengue virus DENV2 16681 non-structural protein 4A/NS4A.

Subcellular location. Endoplasmic reticulum membrane.

Domain organisation. The NG domain region, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which forms a guanosine 5’-triphosphate (GTP)-dependent complex with a homologous NG domain in the signal recognition particle (SRP) complex subunit SRP54. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. GTPase induced rearrangement of SR drives SRP-mediated cotranslational protein translocation into the ER.

Similarity. Belongs to the GTP-binding SRP family.

Isoforms (2)

UniProt ID	Names	Canonical?
P08240-1	1	yes
P08240-2	2

RefSeq proteins (2): NP_001171313, NP_003130* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000897	SRP54_GTPase_dom	Domain
IPR003593	AAA+_ATPase	Domain
IPR007222	SRPRA_N	Domain
IPR011012	Longin-like_dom_sf	Homologous_superfamily
IPR013822	Signal_recog_particl_SRP54_hlx	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036225	SRP/SRP_N	Homologous_superfamily
IPR042101	SRP54_N_sf	Homologous_superfamily

Pfam: PF00448, PF02881, PF04086

Enzyme classification (BRENDA):

• EC 3.6.5.4 — signal-recognition-particle GTPase (BRENDA: 41 organisms, 49 substrates, 10 inhibitors, 41 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.0005–0.1764	36
ATP	0.0249	1

UniProt features (62 total): helix 21, strand 15, modified residue 7, sequence conflict 4, compositionally biased region 4, region of interest 3, binding site 3, turn 2, chain 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2FH5	X-RAY DIFFRACTION	2.45
6Y32	X-RAY DIFFRACTION	2.6
5L3Q	X-RAY DIFFRACTION	3.2
7NFX	ELECTRON MICROSCOPY	3.2
2GO5	ELECTRON MICROSCOPY	7.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08240-F1	74.56	0.34

Functional residue map

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

Ligand- & substrate-binding residues (3): 588–591; 425–432; 520–524

Post-translational modifications (7): 177, 284, 296, 297, 298, 473, 578

Mutagenesis-validated functional residues (1):

Position	Phenotype
407	reduced sr compaction. impaired interaction with srp. impaired detachement from ribosome. does not impair gtp hydrolysis

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 203 (showing top): ELVIDGE_HYPOXIA_DN, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_PROTEIN_TARGETING, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, AMIT_SERUM_RESPONSE_20_MCF10A, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MODULE_149, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, E4F1_Q6, ATF3_Q6, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_DN

GO Biological Process (5): cotranslational protein targeting to membrane (GO:0006613), SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition (GO:0006617), intracellular protein transport (GO:0006886), protein targeting to ER (GO:0045047), SRP-dependent cotranslational protein targeting to membrane (GO:0006614)

GO Molecular Function (7): RNA binding (GO:0003723), GTPase activity (GO:0003924), signal recognition particle binding (GO:0005047), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (5): signal recognition particle receptor complex (GO:0005785), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), extracellular exosome (GO:0070062), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Translation	1
IRE1alpha activates chaperones	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoside triphosphate phosphatase activity	2
protein targeting to membrane	1
SRP-dependent cotranslational protein targeting to membrane	1
protein-containing complex assembly	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
protein targeting	1
establishment of protein localization to endoplasmic reticulum	1
translation	1
cotranslational protein targeting to membrane	1
protein targeting to ER	1
nucleic acid binding	1
ribonucleoprotein complex binding	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
ATP-dependent activity	1
rough endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRPRA	SRPRB	Q9Y5M8	997
SRPRA	SRP54	P13624	895
SRPRA	SRP72	O76094	833
SRPRA	RPL23A	P29316	771
SRPRA	HLA-DPA1	P01905	752
SRPRA	SRP68	Q9UHB9	745
SRPRA	SEC61A1	P38378	742
SRPRA	SHKBP1	Q8TBC3	742
SRPRA	SRP19	P09132	730
SRPRA	SRP9	P49458	681
SRPRA	HLA-B	P01889	663
SRPRA	CD47	Q08722	662
SRPRA	TAP2	Q03519	652
SRPRA	SRP14	P37108	649
SRPRA	SEC62	Q99442	645
SRPRA	SEC63	Q9UGP8	645

IntAct

206 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DDRGK1	UFL1	psi-mi:“MI:0914”(association)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
SRP54	SRPRA	psi-mi:“MI:0407”(direct interaction)	0.560
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
CDK5RAP3	PLD2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SPSB4	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SPANXN3	SRPRA	psi-mi:“MI:0915”(physical association)	0.400
SRPRA	RPL10A	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
HDAC1	TRAK1	psi-mi:“MI:0914”(association)	0.350
KATNA1	KATNBL1	psi-mi:“MI:0914”(association)	0.350
SRPRA	PKD2	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350

BioGRID (416): SRPR (Affinity Capture-MS), SRPR (Affinity Capture-MS), SRPR (Affinity Capture-MS), SRPRB (Co-fractionation), SRPR (Affinity Capture-MS), SRPR (Proximity Label-MS), SRPR (Proximity Label-MS), SRPR (Proximity Label-MS), SRPR (Proximity Label-MS), SRPR (Proximity Label-MS), SRPR (Proximity Label-MS), SRPR (Proximity Label-MS), XIAP (Affinity Capture-MS), ATP2B1 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1CLQ4, A0A139AVY4, A9X4T1, B9FK36, C5E4D9, D0MYB4, G5EES6, J9VQZ9, O14134, O42943, O59672, O93796, O94489, P06625, P08240, P16521, P16638, P25997, P29551, P40024, P43535, P53396, P53585, P53978, Q08972, Q2KJA2, Q2TCH3, Q32PF2, Q3MHE8, Q4HY71, Q5KIM6, Q5R9Z5, Q66H39, Q6MG08, Q75EV6, Q767L0, Q7YR37, Q8H0V6, Q8K268, Q8NE71

Diamond homologs: A0B638, A2STI3, A3DML3, A9CHH2, B0R7X3, B6YSS1, B9LT33, C5A233, D3UJA7, D4GYW6, O07347, O15821, O25458, O27376, O29633, O30391, O32861, O33010, O33013, O43032, O59307, O67066, O67615, O80842, P06625, P08240, P0AGD7, P0AGD8, P0AGD9, P10121, P14929, P20424, P27414, P37105, P37106, P37107, P44518, P44870, P49967, P49968

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SRP54	“up-regulates activity”	SRPRA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 247 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
Metal ion SLC transporters	5	19.0×	4e-04
SHC1 events in ERBB2 signaling	5	15.1×	6e-04
Signaling by ERBB2 TMD/JMD mutants	5	15.1×	6e-04
Signaling by ERBB2 KD Mutants	5	13.4×	9e-04
SRP-dependent cotranslational protein targeting to membrane	15	9.5×	4e-08
R-HSA-425366	8	9.2×	4e-04
Peptide chain elongation	9	7.2×	4e-04
Viral mRNA Translation	9	7.2×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	8	26.9×	2e-07
intracellular zinc ion homeostasis	6	13.8×	7e-04
cell surface receptor protein tyrosine kinase signaling pathway	16	13.3×	9e-11
peptidyl-tyrosine phosphorylation	6	12.1×	1e-03
vascular endothelial growth factor receptor signaling pathway	5	11.5×	6e-03
amino acid transport	6	9.0×	6e-03
cytoplasmic translation	9	8.0×	4e-04
protein autophosphorylation	11	7.7×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	13
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
810840	NM_003139.4(SRPRA):c.1390C>G (p.Gln464Glu)	Pathogenic

SpliceAI

1693 predictions. Top by Δscore:

Variant	Effect	Δscore
11:126264130:T:TA	donor_gain	1.0000
11:126264285:TTGAC:T	acceptor_gain	1.0000
11:126264286:TGAC:T	acceptor_gain	1.0000
11:126264286:TGACC:T	acceptor_gain	1.0000
11:126264287:GAC:G	acceptor_gain	1.0000
11:126264287:GACCT:G	acceptor_gain	1.0000
11:126264288:AC:A	acceptor_gain	1.0000
11:126264288:ACCTG:A	acceptor_gain	1.0000
11:126264289:CC:C	acceptor_gain	1.0000
11:126264289:CCTG:C	acceptor_loss	1.0000
11:126264289:CCTGG:C	acceptor_gain	1.0000
11:126264290:C:CC	acceptor_gain	1.0000
11:126264290:C:CG	acceptor_loss	1.0000
11:126264290:C:T	acceptor_gain	1.0000
11:126264370:TCTCA:T	donor_loss	1.0000
11:126264371:CTCAC:C	donor_loss	1.0000
11:126264372:TCACC:T	donor_loss	1.0000
11:126264373:CACCA:C	donor_loss	1.0000
11:126264375:C:CG	donor_loss	1.0000
11:126264375:CCAG:C	donor_gain	1.0000
11:126264536:CGTG:C	acceptor_gain	1.0000
11:126264538:TG:T	acceptor_gain	1.0000
11:126264539:GCTA:G	acceptor_loss	1.0000
11:126264540:C:CC	acceptor_gain	1.0000
11:126264540:CTAG:C	acceptor_loss	1.0000
11:126264541:T:G	acceptor_loss	1.0000
11:126264944:T:TA	donor_gain	1.0000
11:126264945:C:A	donor_gain	1.0000
11:126264954:TGTA:T	donor_loss	1.0000
11:126264955:GTAC:G	donor_loss	1.0000

AlphaMissense

4206 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:126263929:A:G	L635P	1.000
11:126263965:A:G	L623P	1.000
11:126263979:C:A	Q618H	1.000
11:126263979:C:G	Q618H	1.000
11:126263983:C:A	G617V	1.000
11:126263983:C:T	G617D	1.000
11:126263989:C:T	G615D	1.000
11:126263990:C:G	G615R	1.000
11:126264028:G:A	S602F	1.000
11:126264029:A:G	S602P	1.000
11:126264034:G:T	A600D	1.000
11:126264040:C:T	G598E	1.000
11:126264041:C:G	G598R	1.000
11:126264041:C:T	G598R	1.000
11:126264206:A:C	D591E	1.000
11:126264206:A:T	D591E	1.000
11:126264207:T:A	D591V	1.000
11:126264207:T:C	D591G	1.000
11:126264207:T:G	D591A	1.000
11:126264208:C:G	D591H	1.000
11:126264209:A:C	F590L	1.000
11:126264209:A:T	F590L	1.000
11:126264211:A:G	F590L	1.000
11:126264212:T:A	K589N	1.000
11:126264212:T:G	K589N	1.000
11:126264213:T:A	K589I	1.000
11:126264214:T:C	K589E	1.000
11:126264216:G:A	T588I	1.000
11:126264219:A:G	L587P	1.000
11:126264219:A:T	L587H	1.000

dbSNP variants (sampled 300 via entrez): RS1000086862 (11:126270664 A>T), RS1000108868 (11:126257842 C>A), RS1000137493 (11:126270277 A>G), RS1000176021 (11:126239425 G>A), RS1000207768 (11:126246573 C>G,T), RS1000211101 (11:126250274 G>A), RS1000374053 (11:126244551 C>A), RS1000419633 (11:126253374 G>C,T), RS1000431926 (11:126236862 G>A), RS1000456607 (11:126257366 A>G), RS1000483971 (11:126238139 A>G), RS1000547841 (11:126239780 C>T), RS1000724092 (11:126244213 G>A), RS1000850047 (11:126262266 T>A,C), RS1000902552 (11:126262457 G>A,C)

Disease associations

OMIM: gene MIM:182180 | disease phenotypes: MIM:202700, MIM:260400

GenCC curated gene-disease

Disease	Classification	Inheritance
Shwachman-Diamond syndrome	Moderate	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (4): severe congenital neutropenia (MONDO:0018542), Shwachman-Diamond syndrome 1 (MONDO:0044204), complex neurodevelopmental disorder (MONDO:0100038), Shwachman-Diamond syndrome (MONDO:0009833)

Orphanet (1): Severe congenital neutropenia (Orphanet:42738)

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): CHEMBL4105934 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,656 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL482968	ENMD-2076	2	1,656

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	Kd	8	nM	ENMD-2076

PubChem BioAssay actives

1 with measured affinity, of 208 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
6-(4-methylpiperazin-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(E)-2-phenylethenyl]pyrimidin-4-amine	1425176: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0080	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	affects expression, decreases expression	2
Air Pollutants	increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	decreases methylation, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	decreases expression	1
tetrahydropalmatine	decreases expression	1
methylparaben	increases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases reaction, increases expression	1
ochratoxin A	decreases expression	1
bathocuproine sulfonate	increases expression, affects cotreatment, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
candoxin	increases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acrolein	affects cotreatment, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991889	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01859637	PHASE4	TERMINATED	Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT03333486	PHASE2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT00301834	PHASE2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00909584	PHASE2	TERMINATED	Study of Ezatiostat (Telintra Tablets) for Treatment of Severe Chronic Neutropenia
NCT04844177	PHASE2	UNKNOWN	Total Lymphoid Irradiation Pre-HSCT in Severe Congenital Neutropenia
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00295971	PHASE1	COMPLETED	Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT00176852	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Hemoglobinopathy
NCT00176878	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Bone Marrow Failure Syndromes
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT00499070	Not specified	COMPLETED	Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT02011074	Not specified	COMPLETED	Perioperative Changes of Heart Rate Variability Related to Anxiety and Depressiveness in Patients Undergoing General Anesthesia
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT04275479	Not specified	TERMINATED	Diabetes/ Endocrine Surveillance in SDS
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06056908	Not specified	RECRUITING	Shwachman Diamond Syndrome Registry and Study
NCT06999954	Not specified	RECRUITING	Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform
NCT00305708	PHASE1/PHASE2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases