CFAP95

Summary

CFAP95 (cilia and flagella associated protein 95, HGNC:31422) is a protein-coding gene on chromosome 9q21.12, encoding Cilia- and flagella-associated protein 95 (Q5VTT2). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Predicted to be involved in flagellated sperm motility. Located in axonemal microtubule and plasma membrane.

Source: NCBI Gene 138255 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 11 total
• GTEx eGene: eQTL in 10 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.26 (unconstrained)
• MANE Select transcript: NM_001010940
• Interaction hub: 1,801 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31422
Approved symbol	CFAP95
Name	cilia and flagella associated protein 95
Location	9q21.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204711
Ensembl biotype	protein_coding
Entrez	138255

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000377197

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 1, TSL 5: 1

ENST00000377197, ENST00000466872, ENST00000480564, ENST00000495399, ENST00000527647, ENST00000529131, ENST00000529446, ENST00000936456, ENST00000936457, ENST00000936458, ENST00001060495, ENST00001060496, ENST00001060497, ENST00001060500, ENST00001138511

RefSeq mRNA: 4 — MANE Select: NM_001010940 NM_001010940, NM_001308084, NM_001308085, NM_001308086

CCDS: CCDS35041, CCDS78403

Canonical transcript exons

ENST00000377197 — 6 exons

Exon	Start	End
ENSE00001473067	69905954	69906227
ENSE00001473072	69844517	69844625
ENSE00001473074	69820817	69821031
ENSE00003515718	69856555	69856673
ENSE00003528405	69886838	69886895
ENSE00003639731	69857909	69857977

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 99.28.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5293 / max 151.9756, expressed in 287 samples.

Highest expression (Bgee): bronchial epithelial cell, bronchus, male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa, sperm.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP95 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pituitary	eqtl	1.0e-35	+0.74	9:69803217:C:G
Pancreas	eqtl	1.6e-35	+1.45	9:69820797:C:G
Brain Nucleus accumbens basal ganglia	eqtl	2.2e-17	+1.04	9:69792139:T:C
Testis	eqtl	5.7e-10	+0.20	9:69844651:G:T
Testis	sqtl	6.7e-10	-0.45	9:69844651:G:T
Pituitary	sqtl	7.2e-10	-0.86	9:69844651:G:T
Brain Putamen basal ganglia	eqtl	2.2e-04	-0.44	9:69883553:C:T
Kidney Cortex	eqtl	3.4e-04	+1.36	9:69792139:T:C
Brain Anterior cingulate cortex BA24	eqtl	1.7e-03	+0.63	9:69829308:T:C
Muscle Skeletal	eqtl	3.3e-03	+0.16	9:69873501:C:T
Brain Amygdala	eqtl	6.5e-03	+0.59	9:69792139:T:C
Brain Nucleus accumbens basal ganglia	sqtl	2.1e-02	-0.65	9:69818165:G:A
Lung	sqtl	2.3e-02	-0.43	9:69868731:A:G
Lung	eqtl	2.7e-02	-0.13	9:69823644:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
96847	1.6418	265
96848	0.8875	115

Top tissues by expression

showing 100 of 239 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.28	gold quality
bronchus	UBERON:0002185	98.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.04	gold quality
sperm	CL:0000019	92.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.60	gold quality
right uterine tube	UBERON:0001302	92.09	gold quality
nasal cavity epithelium	UBERON:0005384	90.14	gold quality
epithelium of nasopharynx	UBERON:0001951	89.26	gold quality
oviduct epithelium	UBERON:0004804	87.21	gold quality
pituitary gland	UBERON:0000007	85.47	gold quality
trachea	UBERON:0003126	84.41	gold quality
fallopian tube	UBERON:0003889	83.62	gold quality
left testis	UBERON:0004533	83.33	gold quality
right testis	UBERON:0004534	82.68	gold quality
adenohypophysis	UBERON:0002196	82.49	gold quality
testis	UBERON:0000473	81.84	gold quality
islet of Langerhans	UBERON:0000006	80.54	gold quality
nasal cavity mucosa	UBERON:0001826	80.39	gold quality
caput epididymis	UBERON:0004358	79.08	gold quality
body of tongue	UBERON:0011876	78.23	gold quality
secondary oocyte	CL:0000655	77.48	gold quality
adult organism	UBERON:0007023	76.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.96	gold quality
buccal mucosa cell	CL:0002336	73.56	silver quality
biceps brachii	UBERON:0001507	72.01	gold quality
right lung	UBERON:0002167	70.26	gold quality
tongue	UBERON:0001723	67.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	66.16	gold quality
endometrium	UBERON:0001295	65.27	gold quality
hypothalamus	UBERON:0001898	65.14	gold quality
deltoid	UBERON:0001476	64.92	gold quality
amygdala	UBERON:0001876	62.96	gold quality
oocyte	CL:0000023	62.29	gold quality
superior surface of tongue	UBERON:0007371	61.66	gold quality
left uterine tube	UBERON:0001303	61.61	gold quality
pancreas	UBERON:0001264	61.35	gold quality
gall bladder	UBERON:0002110	60.30	gold quality
stromal cell of endometrium	CL:0002255	60.15	gold quality
caudate nucleus	UBERON:0001873	59.05	gold quality
quadriceps femoris	UBERON:0001377	58.92	silver quality
adult mammalian kidney	UBERON:0000082	58.50	gold quality
lower lobe of lung	UBERON:0008949	58.16	silver quality
Ammon’s horn	UBERON:0001954	58.00	gold quality
metanephros cortex	UBERON:0010533	57.66	gold quality
vastus lateralis	UBERON:0001379	57.47	silver quality
corpus callosum	UBERON:0002336	56.96	gold quality
kidney epithelium	UBERON:0004819	56.66	gold quality
skeletal muscle tissue	UBERON:0001134	56.58	gold quality
lung	UBERON:0002048	56.15	gold quality
pancreatic ductal cell	CL:0002079	55.18	silver quality
substantia nigra	UBERON:0002038	54.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	54.73	gold quality
tibialis anterior	UBERON:0001385	54.71	silver quality
nucleus accumbens	UBERON:0001882	54.67	gold quality
amniotic fluid	UBERON:0000173	54.64	silver quality
muscle tissue	UBERON:0002385	54.35	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	54.06	gold quality
temporal lobe	UBERON:0001871	53.97	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
cerebellar vermis	UBERON:0004720	53.12	gold quality
midbrain	UBERON:0001891	53.10	gold quality
ileal mucosa	UBERON:0000331	53.09	silver quality
metanephros	UBERON:0000081	53.03	gold quality
upper lobe of lung	UBERON:0008948	53.02	gold quality
kidney	UBERON:0002113	52.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	52.90	gold quality
superior vestibular nucleus	UBERON:0007227	52.72	silver quality
upper lobe of left lung	UBERON:0008952	52.68	gold quality
body of pancreas	UBERON:0001150	52.65	gold quality
forebrain	UBERON:0001890	52.43	gold quality
spinal cord	UBERON:0002240	52.02	gold quality
muscle of leg	UBERON:0001383	52.01	gold quality
apex of heart	UBERON:0002098	51.41	gold quality
endocervix	UBERON:0000458	51.08	gold quality
gastrocnemius	UBERON:0001388	50.72	gold quality
rectum	UBERON:0001052	50.59	gold quality
myocardium	UBERON:0002349	50.25	gold quality
brain	UBERON:0000955	49.79	gold quality
uterus	UBERON:0000995	49.68	gold quality
corpus epididymis	UBERON:0004359	48.50	gold quality
putamen	UBERON:0001874	47.40	gold quality
cortex of kidney	UBERON:0001225	47.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.39	gold quality
thymus	UBERON:0002370	45.73	gold quality
anterior cingulate cortex	UBERON:0009835	45.50	gold quality
layer of synovial tissue	UBERON:0007616	45.43	gold quality
cerebral cortex	UBERON:0000956	45.37	gold quality
heart left ventricle	UBERON:0002084	45.21	gold quality
cardiac ventricle	UBERON:0002082	45.13	gold quality
Brodmann (1909) area 46	UBERON:0006483	44.83	gold quality
medulla oblongata	UBERON:0001896	44.79	silver quality
pigmented layer of retina	UBERON:0001782	44.56	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	44.43	gold quality
heart right ventricle	UBERON:0002080	44.34	gold quality
renal medulla	UBERON:0000362	44.16	silver quality
germinal epithelium of ovary	UBERON:0001304	44.00	silver quality
jejunum	UBERON:0002115	43.48	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	61.83
E-HCAD-1	yes	26.59
E-MTAB-10287	yes	25.96
E-MTAB-9388	yes	11.40
E-MTAB-6524	no	70.50
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

48 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Fallopian tube	tissue	34.6
Periaqueductal gray	tissue	19.0
Choroid plexus	tissue	13.8
Testis	tissue	13.3
Medulla oblongata	tissue	12.7
Spinal cord	tissue	12.2
Basal ganglia	tissue	12.0
Hippocampal formation	tissue	11.9
Substantia nigra	tissue	11.8
Septum	tissue	11.7
Corpus callosum	tissue	10.9
Hypothalamus	tissue	10.4
Pons	tissue	10.3
Midbrain	tissue	10.2
Superior colliculi	tissue	9.8
Thalamus	tissue	9.7
Ventral forebrain	tissue	9.2
Cerebral cortex	tissue	8.9
Occipital cortex	tissue	8.9
Putamen	tissue	8.7
Amygdala	tissue	8.1
Prefrontal cortex	tissue	7.7
Motor cortex	tissue	7.7
Entorhinal cortex	tissue	7.6
Somatosensory cortex	tissue	7.6
Temporal cortex	tissue	7.4
Pituitary gland	tissue	7.2
Retrosplenial and cingulate cortex	tissue	7.0
Retrosplenial cortex	tissue	6.7
Olfactory bulb	tissue	6.3
Insular cortex	tissue	6.1
Cerebellum	tissue	4.1
Parathyroid gland	tissue	2.8
Caudate putamen	tissue	2.8
Lung	tissue	2.1
Frontal cortex	tissue	1.8
Gallbladder	tissue	1.3
Kidney	tissue	1.2
Cervix	tissue	0.8
Locus coeruleus	tissue	0.8
Retina	tissue	0.6
Pancreas	tissue	0.5
Endometrium 1	tissue	0.5
Nucleus accumbens	tissue	0.4
Adrenal gland	tissue	0.4
Seminal vesicle	tissue	0.3
Hippocampus	tissue	0.3
Thymus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 98; highest nTPM — Dorsal spinal cord (12.2), Ventral spinal cord (12.2), Dorsal hippocampus (11.9), White matter (10.9), Ventral hippocampus (10.4).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 0.00079, LOEUF 1.26, missense Z -0.173 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000377197 — one region, missense o/e 1.08.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cfap95	ENSMUSG00000033053
rattus_norvegicus	Cfap95	ENSRNOG00000036615

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q32L77	78.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SMC5-DT	ncRNA	100507299
MAMDC2	protein-coding	256691
APBA1	protein-coding	320
PTAR1	protein-coding	375743
CFAP95-DT	ncRNA	494558
MAMDC2-AS1	ncRNA	100507244
SMC5	protein-coding	23137
KLF9	protein-coding	687

Protein

Protein identifiers

Cilia- and flagella-associated protein 95 — Q5VTT2 (reviewed: Q5VTT2)

All UniProt accessions (4): Q5VTT2, E9PIA3, H0YD79, H0YDM9

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with MYH9. Interacts with MYH10.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Flagellum axoneme. Cell membrane.

Tissue specificity. Expressed in undifferentiated embryonic stem cells. Expressed in airway epithelial cells.

Induction. Down-regulated following embryonic stem cells differentiation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VTT2-1	1	yes
Q5VTT2-2	2

RefSeq proteins (4): NP_001010940, NP_001295013, NP_001295014, NP_001295015 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027905	CFAP95	Family

Pfam: PF15139

UniProt features (7 total): topological domain 2, chain 1, transmembrane region 1, region of interest 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7UNG	48-nm repeat of the human respiratory doublet microtubule	ELECTRON MICROSCOPY	3.6
8J07	96nm repeat of human respiratory doublet microtubule and associated axonemal complexes	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTT2-F1	63.03	0.00

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mid piece; principal piece

Antibody reliability (HPA): IH uncertain · IF approved

Functional residue map

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

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	75

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 54 (showing top): SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM, chr9q21, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, RAO_BOUND_BY_SALL4_ISOFORM_B, GOCC_AXONEMAL_MICROTUBULE, GOCC_9PLUS2_MOTILE_CILIUM, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER

GO Biological Process (1): flagellated sperm motility (GO:0030317)

GO Cellular Component (6): cytoplasm (GO:0005737), axonemal microtubule (GO:0005879), plasma membrane (GO:0005886), sperm flagellum (GO:0036126), axonemal A tubule inner sheath (GO:0160111), axoneme (GO:0005930)

GO top-level categories

15 GO namespaces:

Category	Terms
cellular anatomical structure	3
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
intracellular anatomical structure	1
cytoplasmic microtubule	1
axoneme	1
membrane	1
cell periphery	1
9+2 motile cilium	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
cytoskeleton	1
microtubule	1
ciliary plasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 7 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
axonemal microtubule	CC	direct assay
cytoplasm	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 16 of 1,801 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP95	FAM219A	Q8IW50	390
CFAP95	SHC2	P98077	369
CFAP95	MORN5	Q5VZ52	364
CFAP95	DRICH1	Q6PGQ1	361
CFAP95	TPRG1	Q6ZUI0	353
CFAP95	PADI1	Q9ULC6	346
CFAP95	PPDPFL	Q8WWR9	323
CFAP95	FHIP2A	Q5W0V3	315
CFAP95	RSPH14	Q9UHP6	303
CFAP95	HDDC2	Q7Z4H3	293
CFAP95	IGSF3	O75054	287
CFAP95	GANC	Q8TET4	285
CFAP95	DPCD	Q9BVM2	280
CFAP95	GPR176	Q14439	280
CFAP95	LRCH2	Q5VUJ6	275
CFAP95	ODF4	Q2M2E3	275

IntAct

Human interaction partners of CFAP95 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
PB2	physical association	0.370	1

Disease & clinical

Genetic variants

Variant evidence for CFAP95: 11 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	1
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 721):

Position(s)	Effect	Δscore	Sites
9:69844515	acceptor_gain	1.0000
9:69821032–69821033	donor_loss	0.9900	5
9:69844516	acceptor_gain	0.9900
9:69844626–69844630	donor_loss	0.9900	10
9:69886896–69886897	donor_loss	0.9900	5
9:69886900	donor_loss	0.9900	2
9:69905952–69905953	acceptor_loss	0.9900	6
9:69830098	acceptor_gain	0.9800
9:69844515–69844516	acceptor_loss	0.9800	4
9:69844628	donor_loss	0.9800

AlphaMissense

170 missense substitutions predicted likely pathogenic (of 1,502 scored), across 64 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F188	7	0.886	0.969
W202	7	0.842	0.935
W51	7	0.782	0.868
D190	6	0.686	0.751
Y42	5	0.797	0.872
R182	5	0.791	0.894
K183	5	0.743	0.833
G207	5	0.706	0.790
S206	4	0.830	0.891
K195	4	0.759	0.838
G31	4	0.726	0.866
K215	4	0.726	0.835
C184	4	0.685	0.738
D204	4	0.669	0.709
W89	4	0.646	0.683
F136	3	0.867	0.867
F58	3	0.844	0.844
K60	3	0.780	0.804
N200	3	0.779	0.832
S186	3	0.768	0.839

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Lung Adenocarcinoma, Testicular Germ Cell Tumor)

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST005580_291	Intraocular pressure	1e-11
GCST005580_133	Intraocular pressure	2e-10
GCST009310_1	Sensorimotor dexterity	4e-8
GCST011176_10	Stroke	2e-7
GCST009208_5	Transverse temporal cortex volume	4e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0008354	cognitive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
entinostat	increases expression, affects cotreatment	2
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Vorinostat	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.