RSPRY1

Summary

RSPRY1 (ring finger and SPRY domain containing 1, HGNC:29420) is a protein-coding gene on chromosome 16q13, encoding RING finger and SPRY domain-containing protein 1 (Q96DX4).

This gene encodes a glycoprotein that contains a RING-type zinc finger domain and an SPRY domain of unknown function. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 89970 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 211 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 82
• MANE Select transcript: NM_133368

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29420
Approved symbol	RSPRY1
Name	ring finger and SPRY domain containing 1
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1972
Ensembl gene	ENSG00000159579
Ensembl biotype	protein_coding
OMIM	616585
Entrez	89970

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 29 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000394420, ENST00000537866, ENST00000561641, ENST00000562439, ENST00000562768, ENST00000562959, ENST00000563073, ENST00000564435, ENST00000564530, ENST00000566352, ENST00000568505, ENST00000568920, ENST00000860800, ENST00000860801, ENST00000860802, ENST00000860803, ENST00000860804, ENST00000860805, ENST00000860806, ENST00000860807, ENST00000860808, ENST00000860809, ENST00000935122, ENST00000935123, ENST00000935124, ENST00000935125, ENST00000935126, ENST00000935127, ENST00000970574, ENST00000970575, ENST00000970576, ENST00000970577, ENST00000970578, ENST00000970579

RefSeq mRNA: 4 — MANE Select: NM_133368 NM_001305163, NM_001305164, NM_001305182, NM_133368

CCDS: CCDS10775

Canonical transcript exons

ENST00000394420 — 15 exons

Exon	Start	End
ENSE00001046499	57220732	57220847
ENSE00001046505	57216107	57216173
ENSE00001518408	57186329	57186451
ENSE00002583964	57238879	57240469
ENSE00002708658	57204504	57205008
ENSE00003468399	57209075	57209187
ENSE00003499989	57221272	57221415
ENSE00003508818	57231167	57231319
ENSE00003516861	57208058	57208110
ENSE00003598433	57216904	57217035
ENSE00003612004	57235124	57235228
ENSE00003626272	57230711	57230813
ENSE00003631383	57212972	57213098
ENSE00003634527	57227342	57227453
ENSE00003653001	57213888	57213946

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5106 / max 101.0023, expressed in 1812 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154318	15.8794	1809
154319	2.4865	1384
154317	0.1447	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.81	gold quality
nasal cavity epithelium	UBERON:0005384	97.06	gold quality
secondary oocyte	CL:0000655	96.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.12	gold quality
ileal mucosa	UBERON:0000331	96.01	gold quality
oocyte	CL:0000023	94.98	gold quality
sperm	CL:0000019	94.97	gold quality
jejunal mucosa	UBERON:0000399	94.20	gold quality
cardia of stomach	UBERON:0001162	94.16	gold quality
upper arm skin	UBERON:0004263	93.87	gold quality
epithelial cell of pancreas	CL:0000083	93.85	gold quality
ganglionic eminence	UBERON:0004023	93.79	gold quality
nipple	UBERON:0002030	92.78	gold quality
ventricular zone	UBERON:0003053	92.78	gold quality
myocardium	UBERON:0002349	92.67	silver quality
tibialis anterior	UBERON:0001385	92.64	gold quality
cortical plate	UBERON:0005343	92.50	gold quality
adrenal tissue	UBERON:0018303	92.45	gold quality
epithelium of mammary gland	UBERON:0003244	92.33	gold quality
mammary duct	UBERON:0001765	92.28	gold quality
colonic mucosa	UBERON:0000317	92.26	gold quality
bronchial epithelial cell	CL:0002328	92.14	gold quality
vena cava	UBERON:0004087	92.13	silver quality
bronchus	UBERON:0002185	92.08	gold quality
cartilage tissue	UBERON:0002418	92.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.01	silver quality
lower lobe of lung	UBERON:0008949	91.99	gold quality
mammalian vulva	UBERON:0000997	91.79	gold quality
endometrium	UBERON:0001295	91.79	gold quality
oviduct epithelium	UBERON:0004804	91.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting RSPRY1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349

Literature-anchored findings (GeneRIF, showing 3)

• RSPRY1 Mutations are associated with Progressive Skeletal Dysplasia. (PMID:26365341)
• we provide further evidence that Spondyloepimetaphyseal dysplasia Faden-Alkuraya type is a RSPRY1-associated skeletal dysplasia with a distinctive phenotype composed of spondyloepimetaphyseal dysplasia, cono-brachydactyly, and craniosynostosis along with recognizable facial features and intellectual disability. (PMID:30063090)
• Two sisters with RSPRY1-related spondyloepimetaphyseal dysplasia. (PMID:38562122)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rspry1	ENSDARG00000062558
mus_musculus	Rspry1	ENSMUSG00000050079
rattus_norvegicus	Rspry1	ENSRNOG00000060931
caenorhabditis_elegans	F16A11.1	WBGENE00008876

Paralogs (1): RNF123 (ENSG00000164068)

Protein

Protein identifiers

RING finger and SPRY domain-containing protein 1 — Q96DX4 (reviewed: Q96DX4)

All UniProt accessions (5): Q96DX4, H3BPL2, H3BQG6, H3BQQ7, H3BSC7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Disease relevance. Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type (SEMDFA) [MIM:616723] An autosomal recessive skeletal disorder characterized by spondyloepimetaphyseal dysplasia, short stature, facial dysmorphism, short fourth metatarsals, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96DX4-1	1	yes
Q96DX4-2	2

RefSeq proteins (3): NP_001292092, NP_001292093, NP_588609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR035774	SPRY_RSPRY1	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR045129	RNF123/RKP/RSPRY1	Family

Pfam: PF00622, PF13920

UniProt features (12 total): splice variant 2, compositionally biased region 2, signal peptide 1, chain 1, sequence variant 1, domain 1, zinc finger region 1, region of interest 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DX4-F1	84.78	0.74

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 (1): 50

Glycosylation sites (1): 314

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 340 (showing top): RNGTGGGC_UNKNOWN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, COUP_01, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, USF_01, TGIF_01, ZIC1_01, GGGNNTTTCC_NFKB_Q6_01, HNF4_01, AACTTT_UNKNOWN, USF_02, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, EGR1_01, GOBP_PROTEIN_CATABOLIC_PROCESS, TGGAAA_NFAT_Q4_01

GO Biological Process (1): obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (4): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSPRY1	CCDC106	Q9BWC9	595
RSPRY1	EAF1	Q96JC9	593
RSPRY1	CLXN	Q9HAE3	576
RSPRY1	GPATCH3	Q96I76	570
RSPRY1	PRR23C	Q6ZRP0	567
RSPRY1	FIZ1	Q96SL8	562
RSPRY1	ZC3H15	Q8WU90	557
RSPRY1	NUDT13	Q86X67	557
RSPRY1	ZNRF2	Q8NHG8	533
RSPRY1	MRPS34	P82930	528
RSPRY1	TPRA1	Q86W33	528
RSPRY1	METTL6	Q8TCB7	525
RSPRY1	SNX20	Q7Z614	499
RSPRY1	NELFB	Q8WX92	492
RSPRY1	FBXO9	Q9UK97	490

IntAct

96 interactions, top by confidence:

A	B	Type	Score
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
HEY2	ARL10	psi-mi:“MI:0914”(association)	0.640
LYPD3	SCAMP1	psi-mi:“MI:0914”(association)	0.640
VDAC1	HK1	psi-mi:“MI:0914”(association)	0.560
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
GCNT3	BCKDK	psi-mi:“MI:0914”(association)	0.530
CDK5R1	DENR	psi-mi:“MI:0914”(association)	0.530
ITM2A	NDUFB5	psi-mi:“MI:0914”(association)	0.530
SPINK2	STRN	psi-mi:“MI:0914”(association)	0.530
WNT7A	LDLR	psi-mi:“MI:0914”(association)	0.530
RSPRY1	NEFL	psi-mi:“MI:0914”(association)	0.530
SPATA19	MTHFR	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
CLEC3A	ZZEF1	psi-mi:“MI:0914”(association)	0.530
CCNJL	HSPA5	psi-mi:“MI:0914”(association)	0.530
XAGE3	WIZ	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530

BioGRID (124): RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Synthetic Lethality), INF2 (Affinity Capture-MS), C5orf30 (Affinity Capture-MS), NES (Affinity Capture-MS), INA (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS)

ESM2 similar proteins: A1L0Y2, A2ALK8, A2ARP1, A2Z8S0, A4IFG2, A8XT88, B1AVZ0, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4KA23, B4LVS8, B4NKI9, B4PVH6, B4QVW6, M9MRI4, O35242, O76050, P0C644, P26045, Q18223, Q29B63, Q29RQ5, Q3MHZ2, Q3UJK4, Q571F5, Q5M870, Q5NCX5, Q5PQR3, Q5R881, Q6PFW1, Q6PJ21, Q75G68, Q8BVR6, Q8C726, Q8CJC5, Q8R516, Q91YL3, Q91ZY8

Diamond homologs: A0A5F9C6I2, A1L252, A2VD92, B0LPN4, D3ZXK7, E9PZQ0, E9Q401, F1LMY4, O94712, P11716, P16960, P21817, P30957, P69566, Q15413, Q19614, Q1LUS8, Q28FM1, Q5R881, Q5XH91, Q5XPI3, Q5XPI4, Q6VN19, Q8BVR6, Q90WU3, Q92736, Q95LP3, Q96DX4, Q96S59, Q9PTY5, Q9VNV3, A1E2V0, A1L020, A1L3F4, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, E3SCZ8, O08863

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RSPRY1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	67
Likely benign	109
Benign	19

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1029071	NM_133368.3(RSPRY1):c.1422T>A (p.Cys474Ter)	Pathogenic
1706547	NM_133368.3(RSPRY1):c.358G>T (p.Glu120Ter)	Pathogenic
218885	NM_133368.3(RSPRY1):c.1279dup (p.Thr427fs)	Pathogenic
218886	NM_133368.3(RSPRY1):c.121G>T (p.Gly41Cys)	Pathogenic
2427211	NC_000016.9:g.(?57242967)(57243119_?)del	Pathogenic
3391106	NM_133368.3(RSPRY1):c.901_901+15del	Likely pathogenic

SpliceAI

2429 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57207551:A:AG	acceptor_gain	1.0000
16:57209073:A:AG	acceptor_gain	1.0000
16:57209074:G:GG	acceptor_gain	1.0000
16:57209188:G:GG	donor_gain	1.0000
16:57212966:TTTTA:T	acceptor_loss	1.0000
16:57212967:TTTA:T	acceptor_loss	1.0000
16:57212968:TTA:T	acceptor_loss	1.0000
16:57212969:TAG:T	acceptor_loss	1.0000
16:57212970:A:AG	acceptor_gain	1.0000
16:57212970:A:T	acceptor_loss	1.0000
16:57212970:AG:A	acceptor_gain	1.0000
16:57212971:G:A	acceptor_loss	1.0000
16:57212971:G:GG	acceptor_gain	1.0000
16:57212971:GG:G	acceptor_gain	1.0000
16:57212971:GGAT:G	acceptor_gain	1.0000
16:57213094:AGCAG:A	donor_loss	1.0000
16:57213096:CAGG:C	donor_loss	1.0000
16:57213097:AG:A	donor_loss	1.0000
16:57213098:GGT:G	donor_loss	1.0000
16:57213099:G:GC	donor_loss	1.0000
16:57213100:T:A	donor_loss	1.0000
16:57214161:C:G	donor_gain	1.0000
16:57216169:GACAA:G	donor_gain	1.0000
16:57216174:G:GG	donor_gain	1.0000
16:57216995:TC:T	donor_gain	1.0000
16:57217036:G:GG	donor_gain	1.0000
16:57220730:A:AG	acceptor_gain	1.0000
16:57220731:G:GA	acceptor_gain	1.0000
16:57220847:GGTA:G	donor_loss	1.0000
16:57220849:T:G	donor_loss	1.0000

AlphaMissense

3797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57204981:T:C	L108P	1.000
16:57204990:T:A	I111K	1.000
16:57204999:T:C	L114P	1.000
16:57208090:T:C	L128S	1.000
16:57208101:G:C	A132P	1.000
16:57209083:T:A	W138R	1.000
16:57209083:T:C	W138R	1.000
16:57209085:G:C	W138C	1.000
16:57209085:G:T	W138C	1.000
16:57209096:T:A	V142D	1.000
16:57209137:G:A	G156R	1.000
16:57209137:G:C	G156R	1.000
16:57209138:G:A	G156E	1.000
16:57209144:C:A	A158D	1.000
16:57209147:T:A	V159D	1.000
16:57209156:T:C	L162S	1.000
16:57209162:T:C	L164P	1.000
16:57209170:T:C	C167R	1.000
16:57209179:C:T	P170S	1.000
16:57209180:C:A	P170H	1.000
16:57213058:C:A	N201K	1.000
16:57213058:C:G	N201K	1.000
16:57213069:T:A	V205D	1.000
16:57213084:C:A	A210D	1.000
16:57213093:T:C	L213P	1.000
16:57213098:G:C	G215R	1.000
16:57213888:G:A	G215D	1.000
16:57217017:T:A	W295R	1.000
16:57217017:T:C	W295R	1.000
16:57220822:T:C	L331P	1.000

dbSNP variants (sampled 300 via entrez): RS1000131739 (16:57226920 A>G), RS1000159032 (16:57219935 T>C), RS1000256645 (16:57186918 C>G,T), RS1000406513 (16:57212931 G>A), RS1000628241 (16:57198509 T>C), RS1000637311 (16:57192152 G>A), RS1000731564 (16:57189540 C>A), RS1000772954 (16:57192463 A>C,G), RS1000887990 (16:57186140 C>T), RS1000936795 (16:57198222 A>G), RS1001137482 (16:57200965 A>C,G,T), RS1001189925 (16:57204511 A>G,T), RS1001304932 (16:57202680 C>T), RS1001320634 (16:57195104 T>C), RS1001382815 (16:57186273 A>C)

Disease associations

OMIM: gene MIM:616585 | disease phenotypes: MIM:616723

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome	Strong	Autosomal recessive

Mondo (1): progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (MONDO:0014748)

Orphanet (1): Progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (Orphanet:457395)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000598	Abnormality of the ear
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000766	Abnormal sternum morphology
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001363	Craniosynostosis
HP:0001377	Limited elbow extension
HP:0001498	Carpal bone hypoplasia
HP:0001643	Patent ductus arteriosus
HP:0001653	Mitral regurgitation
HP:0001655	Patent foramen ovale
HP:0001761	Pes cavus

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004029_37	Angiotensin-converting enzyme inhibitor intolerance	1.000000e-06
GCST008159_47	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST010396_159	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
beta-lapachone	decreases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation	1
Clozapine	affects cotreatment, increases expression	1
Cuprizone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Lead	affects splicing	1
Manganese	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Valproic Acid	decreases methylation	1
Vanadates	increases expression	1

Clinical trials (associated diseases)

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