RSPH14

Summary

RSPH14 (radial spoke head 14 homolog, HGNC:13437) is a protein-coding gene on chromosome 22q11.22-q11.23, encoding Radial spoke head 14 homolog (Q9UHP6). Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.

This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease.

Source: NCBI Gene 27156 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_014433

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13437
Approved symbol	RSPH14
Name	radial spoke head 14 homolog
Location	22q11.22-q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100218
Ensembl biotype	protein_coding
OMIM	605663
Entrez	27156

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000216036, ENST00000406876, ENST00000421213, ENST00000439064, ENST00000452757

RefSeq mRNA: 1 — MANE Select: NM_014433 NM_014433

CCDS: CCDS13803

Canonical transcript exons

ENST00000216036 — 7 exons

Exon	Start	End
ENSE00000651212	23061809	23061945
ENSE00000651213	23063902	23064133
ENSE00000651216	23134026	23134144
ENSE00000651217	23138840	23138942
ENSE00001154490	23059415	23059718
ENSE00001154494	23140222	23140472
ENSE00001867945	23141949	23141990

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 92.54.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5916 / max 35.1846, expressed in 241 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193303	0.2476	120
193302	0.2080	108
193301	0.1360	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	92.54	gold quality
epithelium of bronchus	UBERON:0002031	91.99	gold quality
bronchus	UBERON:0002185	90.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.27	gold quality
left testis	UBERON:0004533	88.46	gold quality
right testis	UBERON:0004534	88.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.76	gold quality
cortical plate	UBERON:0005343	86.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.32	gold quality
right uterine tube	UBERON:0001302	86.32	gold quality
testis	UBERON:0000473	85.47	gold quality
anterior cingulate cortex	UBERON:0009835	81.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.60	gold quality
cingulate cortex	UBERON:0003027	81.52	gold quality
nucleus accumbens	UBERON:0001882	81.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.82	gold quality
right frontal lobe	UBERON:0002810	79.76	gold quality
caudate nucleus	UBERON:0001873	79.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.97	gold quality
adenohypophysis	UBERON:0002196	78.84	gold quality
putamen	UBERON:0001874	77.97	gold quality
amygdala	UBERON:0001876	77.30	gold quality
pituitary gland	UBERON:0000007	75.57	gold quality
ganglionic eminence	UBERON:0004023	75.47	gold quality
prefrontal cortex	UBERON:0000451	75.41	gold quality
neocortex	UBERON:0001950	75.31	gold quality
islet of Langerhans	UBERON:0000006	75.30	gold quality
epithelium of nasopharynx	UBERON:0001951	75.24	silver quality
nasopharynx	UBERON:0001728	75.23	silver quality
telencephalon	UBERON:0001893	74.88	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

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rsph14	ENSDARG00000017983
mus_musculus	Rsph14	ENSMUSG00000009070
rattus_norvegicus	Rsph14	ENSRNOG00000001315

Protein

Protein identifiers

Radial spoke head 14 homolog — Q9UHP6 (reviewed: Q9UHP6)

Alternative names: Rhabdoid tumor deletion region protein 1

All UniProt accessions (5): Q9UHP6, B5MCI8, H7BZU8, H7C2M5, H7C3W6

UniProt curated annotations — full annotation on UniProt →

Function. Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.

Subunit / interactions. Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Expressed in adult cerebellum, spinal cord, spleen, skeletal muscle and some/5 out of 9 rhabdoid tumors. Detected in fetal brain, lung, liver and kidney.

Similarity. Belongs to the flagellar radial spoke RSP14 family.

RefSeq proteins (1): NP_055248* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR042856	RSP14	Family

Pfam: PF00514

UniProt features (10 total): repeat 8, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHP6-F1	92.73	0.90

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, XU_GH1_EXOGENOUS_TARGETS_UP, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, RFX1_01, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, RATTENBACHER_BOUND_BY_CELF1, GOCC_9PLUS2_MOTILE_CILIUM, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, PTEN_DN.V1_DN, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_129_MOUSE_UP, FOXN3_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (6): radial spoke (GO:0001534), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
axoneme	1
protein-containing complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

1735 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSPH14	RAB36	O95755	979
RSPH14	RAB13	P51153	813
RSPH14	RAB23	Q9ULC3	810
RSPH14	GNAZ	P19086	585
RSPH14	ZNF529	Q6P280	580
RSPH14	TSNAXIP1	Q2TAA8	555
RSPH14	LRRC23	Q53EV4	540
RSPH14	CFAP161	Q6P656	540
RSPH14	ZSWIM2	Q8NEG5	535
RSPH14	CFAP52	Q8N1V2	530
RSPH14	RSPH10B	P0C881	529
RSPH14	CCDC146	Q8IYE0	524
RSPH14	CFAP74	Q9C0B2	524
RSPH14	MAK16	Q9BXY0	509
RSPH14	OR2A2	Q6IF42	506

IntAct

156 interactions, top by confidence:

A	B	Type	Score
AP3M1	RSPH14	psi-mi:“MI:0915”(physical association)	0.830
RSPH14	AP3M1	psi-mi:“MI:0915”(physical association)	0.830
RSPH14	CCDC102B	psi-mi:“MI:0915”(physical association)	0.720
RSPH14	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
KRT31	RSPH14	psi-mi:“MI:0915”(physical association)	0.720
CCDC102B	RSPH14	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	RSPH14	psi-mi:“MI:0915”(physical association)	0.720
AP2M1	RSPH14	psi-mi:“MI:0915”(physical association)	0.670
KRT75	RSPH14	psi-mi:“MI:0915”(physical association)	0.600
RSPH14	TCF4	psi-mi:“MI:0915”(physical association)	0.560
RSPH14	CDR2	psi-mi:“MI:0915”(physical association)	0.560
RSPH14	REL	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	RSPH14	psi-mi:“MI:0915”(physical association)	0.560
RSPH14	KRT40	psi-mi:“MI:0915”(physical association)	0.560
TRIM69	RSPH14	psi-mi:“MI:0915”(physical association)	0.560
RSPH14	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
TCF4	RSPH14	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (64): RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), CCDC102B (Two-hybrid), KRT40 (Two-hybrid), TRIM69 (Two-hybrid), RSPH14 (Two-hybrid), RSPH14 (Two-hybrid), ROPN1L (Affinity Capture-MS), EPHA4 (Affinity Capture-MS)

ESM2 similar proteins: A2AU72, B0F9L4, E9Q912, F1QWA8, O35099, O46563, O75165, O75602, O93614, P0C6R2, P39968, P42345, P42346, P52306, Q04173, Q1RMS6, Q21029, Q5EFZ4, Q5PPZ9, Q5W041, Q5ZL91, Q66L58, Q68FK4, Q6BTZ4, Q6C5Y8, Q6CX49, Q6DD21, Q6FJV1, Q6NUP7, Q6PIY5, Q757R0, Q7YRF1, Q80TR8, Q80W92, Q80WQ2, Q84ZC0, Q8BVE3, Q8BW49, Q8C0Y0, Q8NFP9

Diamond homologs: Q9D3W1, Q9UHP6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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
Formation of the cornified envelope	6	20.3×	1e-04
Keratinization	6	12.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	5	30.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3212 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23061803:CCTCA:C	donor_loss	1.0000
22:23061804:CTCA:C	donor_loss	1.0000
22:23061805:TCA:T	donor_loss	1.0000
22:23061806:CAC:C	donor_loss	1.0000
22:23061807:ACC:A	donor_loss	1.0000
22:23061808:C:A	donor_loss	1.0000
22:23061944:TG:T	acceptor_gain	1.0000
22:23061946:C:CC	acceptor_gain	1.0000
22:23063898:TCA:T	donor_loss	1.0000
22:23063901:CCTGA:C	donor_gain	1.0000
22:23096415:GACA:G	donor_gain	1.0000
22:23096419:G:GG	donor_gain	1.0000
22:23123085:A:AG	acceptor_gain	1.0000
22:23123086:G:GA	acceptor_gain	1.0000
22:23123086:GA:G	acceptor_gain	1.0000
22:23123086:GAGT:G	acceptor_gain	1.0000
22:23123086:GAGTC:G	acceptor_gain	1.0000
22:23140219:CA:C	donor_loss	1.0000
22:23140220:AC:A	donor_loss	1.0000
22:23140221:CCTAT:C	donor_loss	1.0000
22:23140469:CTCA:C	acceptor_gain	1.0000
22:23140470:TCA:T	acceptor_gain	1.0000
22:23140471:CA:C	acceptor_gain	1.0000
22:23140471:CAC:C	acceptor_gain	1.0000
22:23140473:C:CC	acceptor_gain	1.0000
22:23141943:CCTCA:C	donor_loss	1.0000
22:23141944:CTCA:C	donor_loss	1.0000
22:23141945:TCAC:T	donor_loss	1.0000
22:23141946:CA:C	donor_loss	1.0000
22:23141947:ACCT:A	donor_loss	1.0000

AlphaMissense

2277 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23059611:C:G	A300P	0.993
22:23059592:C:G	R306P	0.991
22:23061945:G:C	S218R	0.989
22:23061945:G:T	S218R	0.989
22:23063903:T:G	S218R	0.989
22:23059471:G:C	F346L	0.987
22:23059471:G:T	F346L	0.987
22:23059473:A:G	F346L	0.987
22:23059593:G:T	R306S	0.987
22:23059610:G:T	A300E	0.987
22:23059635:C:G	A292P	0.987
22:23061927:C:A	K224N	0.987
22:23061927:C:G	K224N	0.987
22:23063927:C:G	A210P	0.987
22:23059622:A:T	L296H	0.986
22:23061848:C:G	A251P	0.986
22:23138891:C:G	R84P	0.986
22:23059622:A:G	L296P	0.985
22:23059706:G:T	A268D	0.985
22:23059714:C:A	K265N	0.984
22:23059714:C:G	K265N	0.984
22:23061835:A:G	L255P	0.984
22:23140317:A:G	L35P	0.984
22:23059490:G:T	A340D	0.983
22:23061809:C:G	G264R	0.983
22:23061809:C:T	G264R	0.983
22:23059491:C:G	A340P	0.982
22:23059562:A:G	F316S	0.981
22:23061809:C:A	G264W	0.981
22:23059627:C:A	K294N	0.979

dbSNP variants (sampled 300 via entrez): RS1000012092 (22:23144527 A>T), RS1000017339 (22:23065535 A>C), RS1000029772 (22:23101005 G>A), RS1000063749 (22:23182631 C>G), RS1000079661 (22:23176967 T>C), RS1000101083 (22:23114480 C>G), RS1000165866 (22:23176403 C>G,T), RS1000172899 (22:23138432 A>G), RS1000215930 (22:23176737 C>T), RS1000259754 (22:23150697 G>A), RS1000271390 (22:23071717 G>A,C), RS1000344093 (22:23086903 C>T), RS1000369440 (22:23070718 CAG>C), RS1000403512 (22:23158423 G>A), RS1000413573 (22:23182404 C>A,T)

Disease associations

OMIM: gene MIM:605663 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000175_34	Height	6.000000e-06
GCST003074_24	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	9.000000e-07
GCST003879_4	Serum parathyroid hormone levels	4.000000e-11
GCST007691_23	Femoral neck bone mineral density	2.000000e-07
GCST008818_2	Handedness (Left-handed vs. non-left-handed)	5.000000e-08
GCST008819_3	Handedness (left-handed vs. right-handed)	1.000000e-08
GCST010132_8	Processed meat consumption	5.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement
EFO:0007785	femoral neck bone mineral density
EFO:0009902	handedness
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3788339	GNAZ, RSPH14		0.00	0

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Methapyrilene	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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