CFAP418

Summary

CFAP418 (cilia and flagella associated protein 418, HGNC:27232) is a protein-coding gene on chromosome 8q22.1, encoding Cilia- and flagella-associated protein 418 (Q96NL8). May be involved in photoreceptor outer segment disk morphogenesis.

This gene encodes a ubiquitously expressed protein of unknown function. It has high levels of mRNA expression in the brain, heart, and retina and the protein co-localizes with polyglutamylated tubulin at the base of the primary cilium in human retinal pigment epithelial cells. Mutations in this gene have been associated with autosomal recessive cone-rod dystrophy (arCRD) and retinitis pigmentosa (arRP).

Source: NCBI Gene 157657 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 286 total — 16 pathogenic, 12 likely-pathogenic
• GTEx eGene: eQTL in 44 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 139
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.64 (unconstrained)
• MANE Select transcript: NM_177965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27232
Approved symbol	CFAP418
Name	cilia and flagella associated protein 418
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MOT25, FLJ30600, CORD16, RP64, BBS21, FAP418, SMALLTALK
Ensembl gene	ENSG00000156172
Ensembl biotype	protein_coding
OMIM	614477
Entrez	157657

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

MANE Select: ENST00000286688

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

ENST00000286688, ENST00000945329, ENST00001073463, ENST00001133563

RefSeq mRNA: 2 — MANE Select: NM_177965 NM_001363260, NM_177965

CCDS: CCDS6268

Canonical transcript exons

ENST00000286688 — 6 exons

Exon	Start	End
ENSE00001024972	95263687	95263774
ENSE00001024973	95260468	95260532
ENSE00001088782	95259840	95259905
ENSE00001088784	95252188	95252283
ENSE00001273587	95244913	95247770
ENSE00001294635	95269035	95269201

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 84.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.9874 / max 48.4918, expressed in 1361 samples.

Highest expression (Bgee): secondary oocyte, oviduct epithelium, buccal mucosa cell, mucosa of paranasal sinus, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP418 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 48 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	1.1e-23	-0.99	8:95269252:A:AGGGGACCTGGC
Cells Cultured fibroblasts	eqtl	6.6e-23	+1.70	8:95268514:T:C
Artery Tibial	eqtl	1.4e-21	-0.85	8:95269252:A:AGGGGACCTGGC
Adipose Subcutaneous	eqtl	1.8e-19	-0.76	8:95269252:A:AGGGGACCTGGC
Thyroid	eqtl	1.1e-18	+1.40	8:95268514:T:C
Adipose Visceral Omentum	eqtl	1.4e-18	-0.71	8:95269252:A:AGGGGACCTGGC
Artery Aorta	eqtl	1.7e-17	-0.90	8:95269252:A:AGGGGACCTGGC
Esophagus Gastroesophageal Junction	eqtl	2.9e-16	-0.97	8:95269252:A:AGGGGACCTGGC
Lung	eqtl	1.0e-15	+1.13	8:95268514:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.5e-15	+1.27	8:95268697:C:G
Skin Sun Exposed Lower leg	eqtl	7.8e-15	+1.03	8:95268514:T:C
Esophagus Muscularis	eqtl	1.2e-14	-0.83	8:95269252:A:AGGGGACCTGGC
Colon Sigmoid	eqtl	2.4e-14	-0.96	8:95269252:A:AGGGGACCTGGC
Esophagus Mucosa	eqtl	2.0e-13	+1.03	8:95268514:T:C
Colon Transverse	eqtl	4.0e-12	+0.98	8:95268514:T:C
Heart Atrial Appendage	eqtl	6.8e-10	+0.56	8:95241927:C:T
Liver	eqtl	7.0e-09	+1.53	8:95245287:G:A
Stomach	eqtl	2.1e-08	+1.56	8:95268697:C:G
Muscle Skeletal	eqtl	2.5e-08	-0.31	8:95268845:G:A
Breast Mammary Tissue	eqtl	1.8e-07	-0.29	8:95290861:G:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
94010	1.5135	862
94012	1.2271	714
94011	0.2467	129

Top tissues by expression

showing 100 of 238 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	84.02	gold quality
oviduct epithelium	UBERON:0004804	83.60	gold quality
buccal mucosa cell	CL:0002336	81.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.46	gold quality
bronchial epithelial cell	CL:0002328	79.55	gold quality
epithelium of nasopharynx	UBERON:0001951	79.49	silver quality
bronchus	UBERON:0002185	78.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.24	gold quality
cardiac muscle of right atrium	UBERON:0003379	77.16	gold quality
germinal epithelium of ovary	UBERON:0001304	76.84	gold quality
ventricular zone	UBERON:0003053	76.74	gold quality
pigmented layer of retina	UBERON:0001782	73.85	gold quality
retina	UBERON:0000966	73.83	gold quality
oocyte	CL:0000023	73.58	gold quality
kidney epithelium	UBERON:0004819	72.80	gold quality
fallopian tube	UBERON:0003889	72.40	gold quality
caput epididymis	UBERON:0004358	72.21	gold quality
calcaneal tendon	UBERON:0003701	72.14	gold quality
islet of Langerhans	UBERON:0000006	71.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	71.30	gold quality
ganglionic eminence	UBERON:0004023	71.24	gold quality
smooth muscle tissue	UBERON:0001135	70.74	gold quality
corpus epididymis	UBERON:0004359	70.54	gold quality
gingival epithelium	UBERON:0001949	70.44	gold quality
deltoid	UBERON:0001476	70.32	silver quality
ovary	UBERON:0000992	70.18	gold quality
right uterine tube	UBERON:0001302	69.65	gold quality
left ovary	UBERON:0002119	69.24	gold quality
tibia	UBERON:0000979	69.12	gold quality
adrenal tissue	UBERON:0018303	68.66	gold quality
prefrontal cortex	UBERON:0000451	68.59	gold quality
stromal cell of endometrium	CL:0002255	68.54	gold quality
right ovary	UBERON:0002118	68.51	gold quality
pancreatic ductal cell	CL:0002079	68.31	silver quality
caudate nucleus	UBERON:0001873	67.65	gold quality
right adrenal gland cortex	UBERON:0035827	67.23	gold quality
lymph node	UBERON:0000029	67.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	67.09	gold quality
descending thoracic aorta	UBERON:0002345	66.93	gold quality
left adrenal gland	UBERON:0001234	66.77	gold quality
corpus callosum	UBERON:0002336	66.77	gold quality
right coronary artery	UBERON:0001625	66.68	gold quality
adrenal gland	UBERON:0002369	66.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	66.59	gold quality
body of uterus	UBERON:0009853	66.48	gold quality
left adrenal gland cortex	UBERON:0035825	66.42	gold quality
right adrenal gland	UBERON:0001233	66.37	gold quality
cardiac atrium	UBERON:0002081	66.35	gold quality
nucleus accumbens	UBERON:0001882	66.33	gold quality
heart	UBERON:0000948	66.28	gold quality
popliteal artery	UBERON:0002250	66.19	gold quality
adrenal cortex	UBERON:0001235	66.18	gold quality
tibial artery	UBERON:0007610	66.18	gold quality
muscle tissue	UBERON:0002385	66.13	gold quality
left coronary artery	UBERON:0001626	66.09	gold quality
amygdala	UBERON:0001876	66.03	gold quality
ileal mucosa	UBERON:0000331	65.95	silver quality
heart right ventricle	UBERON:0002080	65.94	silver quality
palpebral conjunctiva	UBERON:0001812	65.93	gold quality
heart left ventricle	UBERON:0002084	65.90	gold quality
aorta	UBERON:0000947	65.87	gold quality
cardiac ventricle	UBERON:0002082	65.84	gold quality
coronary artery	UBERON:0001621	65.83	gold quality
right atrium auricular region	UBERON:0006631	65.81	gold quality
female reproductive system	UBERON:0000474	65.75	gold quality
gingiva	UBERON:0001828	65.68	gold quality
frontal cortex	UBERON:0001870	65.64	gold quality
thoracic aorta	UBERON:0001515	65.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.46	gold quality
nasal cavity epithelium	UBERON:0005384	65.42	gold quality
neocortex	UBERON:0001950	65.39	gold quality
ascending aorta	UBERON:0001496	65.31	gold quality
upper arm skin	UBERON:0004263	65.30	gold quality
putamen	UBERON:0001874	65.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.26	gold quality
forebrain	UBERON:0001890	65.22	gold quality
endometrium	UBERON:0001295	65.21	gold quality
adenohypophysis	UBERON:0002196	65.21	gold quality
placenta	UBERON:0001987	65.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.14	gold quality
pituitary gland	UBERON:0000007	65.10	gold quality
brain	UBERON:0000955	65.06	gold quality
hypothalamus	UBERON:0001898	65.03	gold quality
spinal cord	UBERON:0002240	65.03	gold quality
superficial temporal artery	UBERON:0001614	64.95	gold quality
cerebral cortex	UBERON:0000956	64.89	gold quality
substantia nigra	UBERON:0002038	64.83	gold quality
epithelium of mammary gland	UBERON:0003244	64.82	silver quality
gall bladder	UBERON:0002110	64.76	gold quality
kidney	UBERON:0002113	64.76	gold quality
mammary duct	UBERON:0001765	64.73	silver quality
pancreas	UBERON:0001264	64.71	gold quality
superior frontal gyrus	UBERON:0002661	64.66	gold quality
colonic epithelium	UBERON:0000397	64.64	silver quality
anterior cingulate cortex	UBERON:0009835	64.55	gold quality
temporal lobe	UBERON:0001871	64.52	gold quality
midbrain	UBERON:0001891	64.46	gold quality
skeletal muscle tissue	UBERON:0001134	64.45	gold quality
tonsil	UBERON:0002372	64.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.09

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	38.0
Caudate putamen	tissue	34.4
Septum	tissue	28.0
Periaqueductal gray	tissue	27.1
Basal ganglia	tissue	26.9	not detected
Midbrain	tissue	26.3
Putamen	tissue	26.1
Thalamus	tissue	26.1
Pons	tissue	26.0
Hypothalamus	tissue	25.1
Hippocampal formation	tissue	24.6
Spinal cord	tissue	24.2
Ventral forebrain	tissue	24.2
Superior colliculi	tissue	24.1
Amygdala	tissue	24.0
Medulla oblongata	tissue	23.9
Olfactory bulb	tissue	23.4
Cerebral cortex	tissue	22.4	low
Occipital cortex	tissue	22.4
Substantia nigra	tissue	22.0
Entorhinal cortex	tissue	21.4
Motor cortex	tissue	21.0
Somatosensory cortex	tissue	20.9
Temporal cortex	tissue	20.5
Retrosplenial and cingulate cortex	tissue	20.3
Retrosplenial cortex	tissue	20.0
Prefrontal cortex	tissue	19.7
Insular cortex	tissue	19.6
Corpus callosum	tissue	19.3
Cerebellum	tissue	17.2	not detected
Choroid plexus	tissue	8.3
Nucleus accumbens	tissue	5.3
Retina	tissue	4.7
Hippocampus	tissue	4.6	low
Postcentral gyrus	tissue	4.6
Locus coeruleus	tissue	4.3
Ovary	tissue	3.6	medium
Fallopian tube	tissue	3.6	medium
Parathyroid gland	tissue	3.3	medium
Epididymis	tissue	2.9	medium
Heart muscle	tissue	2.5	medium
Thyroid gland	tissue	2.3	low
Cervix	tissue	2.2	low
Breast	tissue	2.2	medium
Endometrium 1	tissue	2.2	low
Kidney	tissue	2.2	medium
Thymus	tissue	2.2
Pituitary gland	tissue	2.1
Smooth muscle	tissue	2.1	not detected
Lymph node	tissue	2.0	high
Prostate	tissue	1.8	low
Tonsil	tissue	1.8	high
Tongue	tissue	1.7
Placenta	tissue	1.7	low
Liver	tissue	1.7	low
Adrenal gland	tissue	1.7	medium
Testis	tissue	1.6	medium
Seminal vesicle	tissue	1.6	medium
Adipose tissue	tissue	1.6	low
Spleen	tissue	1.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal hippocampus (24.6), Ventral spinal cord (24.2), Dorsal spinal cord (23.5), Subiculum (23.0), Ventral hippocampus (22.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CFAP418 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 116 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973

Functional genomics

gnomAD constraint: pLI 1.76e-05, LOEUF 1.64, missense Z 0.138 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000286688 — one region, missense o/e 1.01. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• In a ciliary-expressed gene (C8orf37), mutations were identified that are associated with autosomal recessive cone-rod dystrophy and retinitis pigmentosa with early macular involvement. (PMID:22177090)
• Mutations in C8orf37 give rise to an early or adolescent-onset autosomal recessive cone rod dystrophy or retinitis pigmentosa phenotype with early macular atrophy. (PMID:23788369)
• Our study identified two novel truncating mutations of the C8orf37 gene in siblings with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia. (PMID:25113443)
• Novel C8orf37 mutations cause retinitis pigmentosa in two consanguineous families of Pakistani origin. (PMID:25802487)
• We conclude that C8orf37 should be added to Bardet-Biedl syndrome (BBS) screening panels as a probable rare cause of the disease and that individuals with C8orf37-related retinal dystrophy should be screened for BBS features. (PMID:26854863)
• This report extends the genotypic spectrum of C8orf37-associated retinal dystrophies and demonstrates for the first time a genotype-phenotype correlation between an arCRD-polydactyly-association and truncating germline mutations affecting the N-terminal region of the protein. (PMID:26865426)
• This is the first functional validation and association of C8ORF37 mutations with the BBS phenotype, which identifies BBS21. The zebrafish studies hereby show that C8ORF37 variants underlie clinically diagnosed BBS-related phenotypes as well as isolated retinal degeneration (PMID:27008867)
• Interactions between C8orf37 and FAM161A, Two Ciliary Proteins Essential for Photoreceptor Survival. (PMID:36233334)
• Disruption of CFAP418 interaction with lipids causes widespread abnormal membrane-associated cellular processes in retinal degenerations. (PMID:37971880)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cfap418	ENSMUSG00000059482
rattus_norvegicus	Cfap418	ENSRNOG00000026672

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914407) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal retina photoreceptor morphology	1
retina degeneration	1
decreased retina photoreceptor cell number	1
decreased exploration in new environment	1
abnormal photoreceptor outer segment morphology	1
abnormal rod electrophysiology	1
abnormal cone electrophysiology	1
thin retina outer nuclear layer	1
short photoreceptor outer segment	1
decreased total retina thickness	1
abnormal electroretinogram waveform feature	1
decreased a-wave amplitude	1
decreased b-wave amplitude	1
increased a-wave implicit time	1
increased b-wave implicit time	1

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	E1BC52	81.6%	Diamond
Danio rerio	P0DOC8	45.5%	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
CFAP418-AS1	ncRNA	100616530
LINC01298	ncRNA	619344
TRS-AGA2-5	tRNA	100189248
MIR3150A	ncRNA	100422964
MIR3150B	ncRNA	100500907
MIR3150BHG	ncRNA	105375650
NDUFAF6	protein-coding	137682
PLEKHF2	protein-coding	79666

Protein

Protein identifiers

Cilia- and flagella-associated protein 418 — Q96NL8 (reviewed: Q96NL8)

All UniProt accessions (1): Q96NL8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in photoreceptor outer segment disk morphogenesis.

Subunit / interactions. Interacts (via N-terminus) with FAM161A (via central region); the interaction is direct.

Subcellular location. Cytoplasm. Photoreceptor inner segment.

Tissue specificity. Widely expressed, with highest levels in heart and brain. Also expressed in the retina (at protein level).

Disease relevance. Cone-rod dystrophy 16 (CORD16) [MIM:614500] An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 64 (RP64) [MIM:614500] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry. Bardet-Biedl syndrome 21 (BBS21) [MIM:617406] A form of Bardet-Biedl syndrome, a syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001350189, NP_808880* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029239	CFAP418	Family

Pfam: PF14996

UniProt features (7 total): sequence variant 3, region of interest 2, chain 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NL8-F1	75.73	0.42

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital disorders of metabolism, Other congenital disorders of metabolism, Eye disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; primary cilium; cell junctions; centrosome; vesicles

Antibody reliability (HPA): IH approved · IF approved

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: 403 (showing top): GOBP_NEUROGENESIS, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, chr8q22, GOBP_PHOTORECEPTOR_CELL_DIFFERENTIATION, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, MARSON_BOUND_BY_FOXP3_STIMULATED, GOCC_CILIARY_BASE, GOCC_PHOTORECEPTOR_INNER_SEGMENT, GOCC_CILIUM, BARX1_TARGET_GENES, BRF1_TARGET_GENES, CHAF1B_TARGET_GENES, DYRK1A_TARGET_GENES

GO Biological Process (1): photoreceptor cell morphogenesis (GO:0008594)

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

GO Cellular Component (3): photoreceptor inner segment (GO:0001917), cytoplasm (GO:0005737), ciliary base (GO:0097546)

GO top-level categories

8 GO namespaces:

Category	Terms
cellular anatomical structure	3
photoreceptor cell development	1
cell morphogenesis involved in neuron differentiation	1
binding	1
intracellular anatomical structure	1
cilium	1
ciliary transition zone	1
ciliary transition fiber	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 5 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
ciliary base	CC	direct assay
cytoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 650 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP418	TTC8	Q8TAM2	728
CFAP418	TULP1	O00294	717
CFAP418	POC1B	Q8TC44	685
CFAP418	BBS1	Q8NFJ9	677
CFAP418	RP1L1	Q8IWN7	669
CFAP418	RAB28	P51157	665
CFAP418	CERKL	Q49MI3	653
CFAP418	OFD1	O75665	648
CFAP418	TTLL5	Q6EMB2	647
CFAP418	CDHR1	Q96JP9	643
CFAP418	BBS2	Q9BXC9	638
CFAP418	BBS10	Q8TAM1	623
CFAP418	BBS5	Q8N3I7	616
CFAP418	PCARE	A6NGG8	604
CFAP418	RPGRIP1	Q96KN7	600

IntAct

Human interaction partners of CFAP418 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

29 partners by confidence:

Partner	Interaction type	MIscore	Records
CAPNS1	physical association	0.530	3
FAM161A	physical association	0.500	5
ANKRD11	physical association	0.370	1
CAMK1D	physical association	0.370	1
CASP8AP2	physical association	0.370	1
CHD3	physical association	0.370	1
CRX	physical association	0.370	1
DAXX	physical association	0.370	1
DDX17	physical association	0.370	1
FRG1	physical association	0.370	1
HIPK2	physical association	0.370	1
HSF2	physical association	0.370	1
MRPS6	physical association	0.370	1
NPL	physical association	0.370	1
PDE4D	physical association	0.370	1
PLEC	physical association	0.370	1
PTK2B	physical association	0.370	1
RBFOX1	physical association	0.370	1
RNF111	physical association	0.370	1
SMARCAD1	physical association	0.370	1
SRC	physical association	0.370	1
SYN3	physical association	0.370	1
SYNCRIP	physical association	0.370	1
THOC5	physical association	0.370	1
TRIM37	physical association	0.370	1
TXNRD2	physical association	0.370	1
ZNF106	physical association	0.370	1
CST6	physical association	0.000	1
XPNPEP3	physical association	0.000	1

Disease & clinical

Genetic variants

Variant evidence for CFAP418: 286 ClinVar records (28 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	12
Uncertain significance	141
Likely benign	66
Benign	8

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 28 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
631535	NM_177965.4(CFAP418):c.16_19del (p.Asp6fs)	Pathogenic	criteria provided, single submitter	1
930729	NM_177965.4(CFAP418):c.363del (p.Asn121fs)	Pathogenic	criteria provided, single submitter	1
956772	NM_177965.4(CFAP418):c.177dup (p.Glu60fs)	Pathogenic	criteria provided, single submitter	1
1179152	NM_177965.4(CFAP418):c.124del (p.Arg42fs)	Pathogenic	criteria provided, single submitter	1
1681127	NM_177965.4(CFAP418):c.349_353del (p.Gly117fs)	Pathogenic	criteria provided, single submitter	1
1681132	NM_177965.4(CFAP418):c.298dup (p.Leu100fs)	Pathogenic	criteria provided, single submitter	1
1681150	NM_177965.4(CFAP418):c.104del (p.Gly35fs)	Pathogenic	criteria provided, single submitter	1
1681151	NM_177965.4(CFAP418):c.89_99del (p.Pro30fs)	Pathogenic	criteria provided, single submitter	1
1681158	NM_177965.4(CFAP418):c.19G>T (p.Glu7Ter)	Pathogenic	criteria provided, single submitter	1
2089115	NM_177965.4(CFAP418):c.187_188insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGGCGAGGCGGGCGGATCACGAGGTCAGGANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAAAGAAGATGATC (p.Asp62_Leu63insArgProGlyAlaValAlaHisAlaCysAsnProSerThrLeuGlyGlyArgGlyGlyArgIleThrArgSerGlyXaaXaaXaaXaaLysLysLysLysLysLysLysLysGluAspAsp)	Pathogenic	criteria provided, single submitter	1
4774335	NM_177965.4(CFAP418):c.484del (p.Glu162fs)	Pathogenic	criteria provided, single submitter	1
4901109	NM_177965.4(CFAP418):c.375-1G>C	Pathogenic	criteria provided, single submitter	1
3358696	NM_177965.4(CFAP418):c.243+3A>C	Likely pathogenic	criteria provided, single submitter	2
684431	NM_177965.4(CFAP418):c.240del (p.Ser81fs)	Likely pathogenic	criteria provided, single submitter	1
684432	NM_177965.4(CFAP418):c.130C>T (p.Gln44Ter)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CFAP418’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 566):

Position(s)	Effect	Δscore	Sites
8:95259939	acceptor_gain	1.0000
8:95260466–95260467	donor_loss	1.0000	4
8:95263685–95263686	donor_loss	1.0000	5
8:95252186–95252187	donor_loss	0.9900	4
8:95259912	acceptor_gain	0.9900
8:95259923	acceptor_gain	0.9900
8:95259933	acceptor_gain	0.9900
8:95260467	donor_loss	0.9900
8:95260533–95260534	acceptor_loss	0.9900	6
8:95263775–95263776	acceptor_loss	0.9900	6

AlphaMissense

336 missense substitutions predicted likely pathogenic (of 1,377 scored), across 82 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
D136	8	0.902	0.974
H207	8	0.866	0.945
F156	8	0.783	0.977
N158	8	0.782	0.931
W147	7	0.986	0.997
C135	7	0.983	0.989
W202	7	0.979	0.997
C132	7	0.977	0.993
C183	7	0.970	0.988
C181	7	0.969	0.988
C204	7	0.955	0.974
C127	7	0.953	0.973
R157	7	0.950	0.995
C104	7	0.949	0.970
F155	7	0.947	0.986
W185	7	0.898	0.979
Q182	7	0.863	0.974
F137	7	0.853	0.964
G117	6	0.862	0.932
P161	6	0.820	0.907

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000154

Disease associations

OMIM: gene MIM:614477 | disease phenotypes: MIM:614500, MIM:268000, MIM:617406

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
cone-rod dystrophy 16	Definitive	Autosomal recessive	3
bardet-biedl syndrome 21	Definitive	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Ophthalmological ciliopathies	green
Rare multisystem ciliopathy Super panel	green
Retinal disorders	green
Bardet Biedl syndrome	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber

Mondo (5): cone-rod dystrophy 16 (MONDO:0013786), retinitis pigmentosa (MONDO:0019200), bardet-biedl syndrome 21 (MONDO:0044308), retinitis pigmentosa 64 (MONDO:0800359), inherited retinal dystrophy (MONDO:0019118)

Orphanet (2): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

showing 60 of 139 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000548	Cone/cone-rod dystrophy
HP:0000551	Color vision defect
HP:0000556	Retinal dystrophy
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000668	Hypodontia
HP:0000678	Dental crowding
HP:0000691	Microdontia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000717	Autism
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000789	Infertility
HP:0000818	Abnormality of the endocrine system

GWAS associations

1 associations:

Study	Trait	p-value
GCST001762_566	Obesity-related traits	7e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004810	interleukin-6 measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

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
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
MT19c compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Folic Acid	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

showing 60 of 238 trials:

NCT	Phase	Status	Title
NCT00717080	Phase 4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	Phase 3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	Phase 3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	Phase 3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	Phase 3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	Phase 3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	Phase 3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	Phase 3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	Phase 3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	Phase 3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	Phase 3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	Phase 3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT07710196	Phase 3	NOT_YET_RECRUITING	A 24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	Phase 2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	Phase 2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	Phase 2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	Phase 2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	Phase 2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	Phase 2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	Phase 2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	Phase 2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	Phase 2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	Phase 2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	Phase 2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	Phase 2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	Phase 2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	Phase 2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	Phase 2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	Phase 2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	Phase 2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	Phase 2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	Phase 2	ACTIVE_NOT_RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	Phase 2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	Phase 2	ACTIVE_NOT_RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT07796646	Phase 2	NOT_YET_RECRUITING	Study to Evaluate the Long-Term Safety of Ultevursen in Participants With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT00063765	Phase 1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	Phase 1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	Phase 1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	Phase 1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT01482195	Phase 1	COMPLETED	Trial of Subretinal Injection of (rAAV2-VMD2-hMERTK)
NCT01531348	Phase 1	COMPLETED	Intravitreal Injection of MSCs in Retinitis Pigmentosa
NCT01543906	Phase 1	COMPLETED	Oral QLT091001 in Retinitis Pigmentosa (RP) Subjects With an Autosomal Dominant Mutation in Retinal Pigment Epithelial 65 Protein (RPE65)
NCT01604356	Phase 1	COMPLETED	Acupuncture for the Treatment of Vision Loss Due to Retinitis Pigmentosa
NCT01736059	Phase 1	ACTIVE_NOT_RECRUITING	Clinical Trial of Autologous Intravitreal Bone-marrow CD34+ Stem Cells for Retinopathy
NCT02280135	Phase 1	COMPLETED	Clinical Trial of Intravitreal Injection of Autologous Bone Marrow Stem Cells in Patients With Retinitis Pigmentosa
NCT03063021	Phase 1	COMPLETED	The FIGHT-RP1 Study
NCT03772938	Phase 1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT03944239	Phase 1	ACTIVE_NOT_RECRUITING	Safety and Efficacy of Subretinal Transplantation of Clinical Human Embryonic Stem Cell Derived Retinal Pigment Epitheliums in Treatment of Retinitis Pigmentosa
NCT03999021	Phase 1	ACTIVE_NOT_RECRUITING	FIGHT-RP 1 Extension Study
NCT04284293	Phase 1	ACTIVE_NOT_RECRUITING	CNS10-NPC for the Treatment of RP
NCT04925687	Phase 1	COMPLETED	Phase 1 Study of Intravitreal Autologous CD34+ Stem Cell Therapy for Retinitis Pigmentosa
NCT05147701	Phase 1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT06291935	Phase 1	RECRUITING	Safety and Tolerability of Intravitreal Administration of VG901 in Patients With Retinitis Pigmentosa Due to Mutations in the CNGA1 Gene
NCT06319872	Phase 1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06460844	Phase 1	ACTIVE_NOT_RECRUITING	Study to Evaluate Safety of RTx-015 Injection in Retinitis Pigmentosa or Choroideremia Patients (ENVISION)
NCT06936787	Phase 1	RECRUITING	An Open-label, Dose-ascending Study of IGT001 for Retinitis Pigmentosa
NCT07774975	Phase 1	NOT_YET_RECRUITING	Safety Evaluation Study of Pitavastatin PLGA Nano-particle for Retinitis Pigmentosa