SRP68

Summary

SRP68 (signal recognition particle 68, HGNC:11302) is a protein-coding gene on chromosome 17q25.1, encoding Signal recognition particle subunit SRP68 (Q9UHB9). Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). It is a common-essential gene (DepMap: required in 92.3% of cancer cell lines).

This gene encodes a subunit of the signal recognition particle (SRP). The SRP is a ribonucleoprotein complex that transports secreted and membrane proteins to the endoplasmic reticulum for processing. The complex includes a 7S RNA and six protein subunits. The encoded protein is the 68kDa component of the SRP, and forms a heterodimer with the 72kDa subunit that is required for SRP function. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and three pseudogenes of this gene are located within the Smith-Magenis syndrome region on chromosome 17.

Source: NCBI Gene 6730 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neutropenia, severe congenital, 10, autosomal recessive (Moderate, GenCC)
• Clinical variants (ClinVar): 87 total
• Phenotypes (HPO): 9
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 92.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_014230

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11302
Approved symbol	SRP68
Name	signal recognition particle 68
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167881
Ensembl biotype	protein_coding
OMIM	604858
Entrez	6730

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 6 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000307877, ENST00000539137, ENST00000542536, ENST00000585539, ENST00000586859, ENST00000587864, ENST00000588643, ENST00000588736, ENST00000590833, ENST00000591272, ENST00000592704, ENST00000602720, ENST00000909201, ENST00000909202, ENST00000936368

RefSeq mRNA: 3 — MANE Select: NM_014230 NM_001260502, NM_001260503, NM_014230

CCDS: CCDS11738, CCDS58600, CCDS58601

Canonical transcript exons

ENST00000307877 — 16 exons

Exon	Start	End
ENSE00002228999	76070378	76070444
ENSE00002798223	76072308	76072517
ENSE00002970041	76038785	76039933
ENSE00003469201	76060308	76060390
ENSE00003494525	76061492	76061574
ENSE00003509886	76057403	76057543
ENSE00003525784	76043829	76043958
ENSE00003541870	76045292	76045386
ENSE00003583311	76063976	76064171
ENSE00003601652	76046038	76046194
ENSE00003619803	76050428	76050526
ENSE00003624349	76067217	76067330
ENSE00003630602	76047906	76047970
ENSE00003646258	76061110	76061219
ENSE00003655591	76040903	76040978
ENSE00003686383	76040419	76040474

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.3551 / max 553.9949, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168159	56.1339	1822
168157	0.1375	81
168156	0.0837	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	98.53	gold quality
upper arm skin	UBERON:0004263	97.20	gold quality
deltoid	UBERON:0001476	96.95	gold quality
ileal mucosa	UBERON:0000331	96.94	gold quality
body of pancreas	UBERON:0001150	96.71	gold quality
gastrocnemius	UBERON:0001388	96.55	gold quality
sural nerve	UBERON:0015488	96.45	gold quality
islet of Langerhans	UBERON:0000006	96.21	gold quality
muscle of leg	UBERON:0001383	96.16	gold quality
pancreas	UBERON:0001264	96.15	gold quality
skin of leg	UBERON:0001511	96.11	gold quality
skin of abdomen	UBERON:0001416	96.10	gold quality
kidney epithelium	UBERON:0004819	96.09	gold quality
esophagus mucosa	UBERON:0002469	95.97	gold quality
muscle organ	UBERON:0001630	95.88	gold quality
skeletal muscle organ	UBERON:0014892	95.88	gold quality
esophagus squamous epithelium	UBERON:0006920	95.81	gold quality
cartilage tissue	UBERON:0002418	95.76	gold quality
zone of skin	UBERON:0000014	95.65	gold quality
lower esophagus mucosa	UBERON:0035834	95.51	gold quality
ventricular zone	UBERON:0003053	95.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.50	gold quality
esophagus	UBERON:0001043	95.44	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.40	gold quality
smooth muscle tissue	UBERON:0001135	95.25	gold quality
adenohypophysis	UBERON:0002196	95.17	gold quality
skeletal muscle tissue	UBERON:0001134	95.13	gold quality
ectocervix	UBERON:0012249	95.07	gold quality
stromal cell of endometrium	CL:0002255	95.01	gold quality
popliteal artery	UBERON:0002250	94.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

53 targeting SRP68, 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-3185	99.99	68.12	1959
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4720-3P	98.50	68.88	988

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 92.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• The RNA binding domain of SRP68 included residues from positions 52 to 252. Ninety-four amino acids near the C terminus of SRP68 mediated the binding to SRP72 (PMID:16672232)
• SRP68/72 heterodimers as major nuclear proteins whose binding of histone H4 tail is inhibited by H4R3 methylation. (PMID:23048028)
• study presents the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19; data provide the structural basis for eukaryote-specific, SRP68-driven RNA remodeling required for protein translocation (PMID:24700861)
• The crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP have been presented. (PMID:27899666)
• The essential role of the SRP68-SRP72 interaction in the signal recognition particle-mediated protein translocation (PMID:28369529)
• e show that SRP RNA does not bind to the ribosome, while SRP binds with nanomolar affinity involving a two-step mechanism of the key-player SRP54. Ultrasensitive binding of SRP68/72 indicates avidity by multiple binding sites that are dominated by the C-terminus of SRP72 (PMID:30649417)
• Identification of biallelic germline variants of SRP68 in a sporadic case with severe congenital neutropenia. (PMID:32273475)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	srp68	ENSDARG00000020820
mus_musculus	Srp68	ENSMUSG00000020780
rattus_norvegicus	Srp68	ENSRNOG00000009351
drosophila_melanogaster	Srp68	FBGN0035947
caenorhabditis_elegans		WBGENE00010097

Protein

Protein identifiers

Signal recognition particle subunit SRP68 — Q9UHB9 (reviewed: Q9UHB9)

Alternative names: Signal recognition particle 68 kDa protein

All UniProt accessions (3): Q9UHB9, K7EN53, K7EQC2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER. The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER. Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently. The SRP complex possibly participates in the elongation arrest function.

Subunit / interactions. Heterodimer with SRP72. SRP68/SRP72 heterodimer formation is stabilized by the presence of 7SL RNA. Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9. Within the SRP complex, interacts (via C-terminus) with SRP72 (via N-terminus).

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Endoplasmic reticulum.

Disease relevance. Neutropenia, severe congenital, 10, autosomal recessive (SCN10) [MIM:620534] A form of severe congenital neutropenia, a disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l, and early onset of severe bacterial infections. SCN10 is characterized by infantile onset of neutropenia. Anemia and thrombocytopenia may be transiently present. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminus is required for RNA-binding.

Similarity. Belongs to the SRP68 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UHB9-1	1	yes
Q9UHB9-2	2
Q9UHB9-3	3
Q9UHB9-4	4

RefSeq proteins (3): NP_001247431, NP_001247432, NP_055045* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026258	SRP68	Family
IPR034652	SRP68-RBD	Domain
IPR038253	SRP68_N_sf	Homologous_superfamily

Pfam: PF16969

UniProt features (38 total): helix 12, mutagenesis site 6, sequence conflict 5, region of interest 3, splice variant 3, modified residue 3, turn 2, compositionally biased region 2, chain 1, strand 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5M72	X-RAY DIFFRACTION	1.6
4P3F	X-RAY DIFFRACTION	1.7
5WRV	X-RAY DIFFRACTION	1.7
8QVX	ELECTRON MICROSCOPY	2.7
7QWQ	ELECTRON MICROSCOPY	2.83
8QVW	ELECTRON MICROSCOPY	3
7NFX	ELECTRON MICROSCOPY	3.2
5M73	X-RAY DIFFRACTION	3.4
4P3E	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHB9-F1	80.14	0.42

Functional residue map

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

Post-translational modifications (3): 48, 241, 452

Mutagenesis-validated functional residues (6):

Position	Phenotype
86	loss of interaction with srp72.
590	loss of interaction with srp72. diminished localization to endoplasmic reticulum.
592	loss of interaction with srp72.
598	loss of interaction with srp72; when associated with a-56 in srp72.
600	loss of interaction with srp72.
609	reduced interaction with srp72.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 158 (showing top): GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, WANG_LMO4_TARGETS_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_LOCALIZATION_WITHIN_MEMBRANE, DANG_BOUND_BY_MYC, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOCC_RIBOSOME, GOCC_NUCLEOLUS, GOCC_RIBONUCLEOPROTEIN_COMPLEX, BENPORATH_MYC_MAX_TARGETS

GO Biological Process (2): SRP-dependent cotranslational protein targeting to membrane (GO:0006614), response to xenobiotic stimulus (GO:0009410)

GO Molecular Function (7): RNA binding (GO:0003723), signal recognition particle binding (GO:0005047), 7S RNA binding (GO:0008312), protein domain specific binding (GO:0019904), endoplasmic reticulum signal sequence receptor activity (GO:0030942), protein binding (GO:0005515), ribosome binding (GO:0043022)

GO Cellular Component (10): nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), signal recognition particle, endoplasmic reticulum targeting (GO:0005786), cytosol (GO:0005829), ribosome (GO:0005840), focal adhesion (GO:0005925), signal recognition particle (GO:0048500), nucleus (GO:0005634), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
ribonucleoprotein complex binding	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
translation	1
cotranslational protein targeting to membrane	1
protein targeting to ER	1
response to chemical	1
nucleic acid binding	1
RNA binding	1
protein binding	1
signal sequence receptor activity	1
binding	1
nuclear lumen	1
endomembrane system	1
signal recognition particle	1
cell-substrate junction	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

2025 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRP68	SRP14	P37108	999
SRP68	SRP9	P49458	999
SRP68	SRP72	O76094	999
SRP68	SRP19	P09132	999
SRP68	SRP54	P13624	999
SRP68	SRPRB	Q9Y5M8	853
SRP68	SRPRA	P08240	745
SRP68	SPCS2	Q15005	595
SRP68	SEC61A1	P38378	592
SRP68	SEC63	Q9UGP8	570
SRP68	SPCS1	Q9Y6A9	491
SRP68	SEC62	Q99442	476
SRP68	RPL23A	P29316	441
SRP68	ALG14	Q96F25	430
SRP68	CDIP1	Q9H305	413

IntAct

178 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
SRP72	SRP68	psi-mi:“MI:0407”(direct interaction)	0.730
SRP72	SRP68	psi-mi:“MI:0915”(physical association)	0.730
SRP9	SRP72	psi-mi:“MI:0914”(association)	0.730
SRP68	SRP72	psi-mi:“MI:0914”(association)	0.730
SRP19	SRP68	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GBA2	ILVBL	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
SRP14	PPM1G	psi-mi:“MI:0914”(association)	0.640
EPB41L2	AP3B1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
H1-4	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
SRP68	MAGEB2	psi-mi:“MI:0914”(association)	0.530
RPL7A	NVL	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
CFTR	SRP68	psi-mi:“MI:0915”(physical association)	0.520
	AP3D1	psi-mi:“MI:0914”(association)	0.460
	MYL12B	psi-mi:“MI:0914”(association)	0.460

BioGRID (531): SRP68 (Affinity Capture-MS), SRP68 (Affinity Capture-MS), RPL31 (Co-fractionation), SRP68 (Co-fractionation), SRP68 (Co-fractionation), SRP68 (Co-fractionation), SRP68 (Co-fractionation), SRP68 (Co-fractionation), SRP68 (Co-fractionation), SRP68 (Affinity Capture-MS), SRP68 (Affinity Capture-MS), SRP68 (Proximity Label-MS), SRP68 (Affinity Capture-MS), SRP68 (Affinity Capture-MS), SRP68 (Affinity Capture-MS)

ESM2 similar proteins: A1Z3X3, A2AT37, A2VD00, A4GWN3, A4II09, A4VCH4, A7RWP6, B0W6N3, O43395, O49160, O75937, P23116, P32780, P46940, Q00004, Q14152, Q173M7, Q1JU68, Q2HJ41, Q2KIA6, Q40554, Q5EAV6, Q5R5F1, Q5RE03, Q5ZJ85, Q5ZMW3, Q62383, Q642C0, Q6DDM4, Q6GMH0, Q6GQ80, Q6NZB0, Q6PCR7, Q7KZ85, Q7ZY79, Q8BM39, Q8BMA6, Q8UVK2, Q8VZM1, Q922U1

Diamond homologs: Q00004, Q20822, Q8BMA6, Q9UHB9, Q9VSS2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRP72	“up-regulates activity”	SRP68	binding
SRP19	“up-regulates activity”	SRP68	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 191 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
Peptide chain elongation	20	18.8×	1e-18
Viral mRNA Translation	20	18.8×	1e-18
Eukaryotic Translation Termination	21	18.7×	4e-19
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	20	18.6×	1e-18
SRP-dependent cotranslational protein targeting to membrane	25	18.6×	2e-22
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	21	18.3×	5e-19
Response of EIF2AK4 (GCN2) to amino acid deficiency	22	18.1×	2e-19
Selenocysteine synthesis	20	17.8×	3e-18

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	21	23.0×	4e-20
ribosomal large subunit biogenesis	7	18.4×	3e-05
translation	23	14.0×	3e-17
mRNA stabilization	5	10.8×	9e-03
ribosomal small subunit biogenesis	8	10.8×	2e-04
mRNA transport	6	9.3×	6e-03
negative regulation of translation	8	9.3×	5e-04
rRNA processing	10	8.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2653 predictions. Top by Δscore:

Variant	Effect	Δscore
17:76040414:CTTA:C	donor_loss	1.0000
17:76040415:TTA:T	donor_loss	1.0000
17:76040416:TACC:T	donor_loss	1.0000
17:76040417:A:AC	donor_gain	1.0000
17:76040417:AC:A	donor_gain	1.0000
17:76040418:C:CA	donor_loss	1.0000
17:76040418:C:CC	donor_gain	1.0000
17:76040418:CC:C	donor_gain	1.0000
17:76040418:CCTT:C	donor_gain	1.0000
17:76040418:CCTTA:C	donor_gain	1.0000
17:76040482:T:C	acceptor_gain	1.0000
17:76040979:C:CC	acceptor_gain	1.0000
17:76043826:CACC:C	donor_loss	1.0000
17:76043827:A:C	donor_loss	1.0000
17:76043828:CCTTT:C	donor_loss	1.0000
17:76043954:AACAC:A	acceptor_gain	1.0000
17:76043956:CAC:C	acceptor_gain	1.0000
17:76045286:CGTTA:C	donor_loss	1.0000
17:76045287:GTTA:G	donor_loss	1.0000
17:76045288:TTA:T	donor_loss	1.0000
17:76045289:TACCT:T	donor_loss	1.0000
17:76045290:AC:A	donor_loss	1.0000
17:76045385:TT:T	acceptor_gain	1.0000
17:76045387:C:CC	acceptor_gain	1.0000
17:76045395:CAGA:C	acceptor_gain	1.0000
17:76045398:A:AC	acceptor_gain	1.0000
17:76045398:A:C	acceptor_gain	1.0000
17:76046195:C:CC	acceptor_gain	1.0000
17:76050423:CCTA:C	donor_loss	1.0000
17:76050424:CTA:C	donor_loss	1.0000

AlphaMissense

4105 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:76039809:G:T	A594D	1.000
17:76046156:C:G	R394P	1.000
17:76057489:A:G	W298R	1.000
17:76057489:A:T	W298R	1.000
17:76061202:A:G	L221P	1.000
17:76061552:C:T	G195E	1.000
17:76061553:C:G	G195R	1.000
17:76061553:C:T	G195R	1.000
17:76063981:C:G	A186P	1.000
17:76064053:C:G	A162P	1.000
17:76064061:A:G	L159P	1.000
17:76064077:G:C	H154D	1.000
17:76064115:A:G	L141P	1.000
17:76064129:G:C	S136R	1.000
17:76064129:G:T	S136R	1.000
17:76064131:T:G	S136R	1.000
17:76064134:A:G	W135R	1.000
17:76064134:A:T	W135R	1.000
17:76067298:C:G	R95P	1.000
17:76067301:A:G	L94P	1.000
17:76067304:C:G	R93P	1.000
17:76067312:T:A	R90S	1.000
17:76067312:T:G	R90S	1.000
17:76067321:A:C	C87W	1.000
17:76067322:C:T	C87Y	1.000
17:76070378:C:A	R84M	1.000
17:76070382:A:C	Y83D	1.000
17:76070382:A:G	Y83H	1.000
17:76070383:C:A	R82S	1.000
17:76070383:C:G	R82S	1.000

dbSNP variants (sampled 300 via entrez): RS1000070502 (17:76066577 A>C), RS1000206025 (17:76069564 G>A), RS1000258651 (17:76038556 T>C), RS1000358849 (17:76048228 C>T), RS1000394907 (17:76038406 G>A,T), RS1000405460 (17:76068751 A>G), RS1000512849 (17:76074359 A>T), RS1000752354 (17:76042786 T>C), RS1000929308 (17:76072066 C>A,T), RS1000939448 (17:76050176 T>C), RS1000968071 (17:76064946 G>A), RS1001010955 (17:76056536 G>A), RS1001062852 (17:76042823 G>A,C), RS1001172936 (17:76068299 A>T), RS1001288804 (17:76068109 T>A,C)

Disease associations

OMIM: gene MIM:604858 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neutropenia, severe congenital, 10, autosomal recessive	Moderate	Autosomal recessive

Mondo (1): neutropenia, severe congenital, 10, autosomal recessive (MONDO:0957809)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001903	Anemia
HP:0003593	Infantile onset
HP:0012136	Dysplastic granulopoesis
HP:0012311	Increased total monocyte count
HP:0033150	Anorectal abscess
HP:0033607	Bone marrow arrest at the promyelocytic stage

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066313 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.73	Kd	18.81	nM	CHEMBL5653589
7.73	ED50	18.81	nM	CHEMBL5653589
5.39	Kd	4087	nM	CHEMBL3752910
5.39	ED50	4087	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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	2149485: Binding affinity to human SRP68 incubated for 45 mins by Kinobead based pull down assay	kd	0.0188	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149485: Binding affinity to human SRP68 incubated for 45 mins by Kinobead based pull down assay	kd	4.0873	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects expression, increases abundance, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
testosterone undecanoate	increases expression	1
tetrahydropalmatine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Arsenic	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	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
CHEMBL5652527	Binding	Binding affinity to human SRP68 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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3I5	Abcam HEK293T SRP68 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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